Method of treating or preventing osteoporosis comprising administering to a patient in need thereof an effective amount of pharmacuetical composition comprising benzamidine derivative or it&#39;s salt, and bisphosphonate

ABSTRACT

The present invention provides a method of treating or preventing osteoporosis comprising administering to a patient in need thereof an effective amount of pharmaceutical composition comprising benzamidine derivative or its salt, and bisphosphonate for the purpose of using simultaneously, separately, or sequentially as active ingredients. As a prophylactic or therapeutic composition for osteoporosis, the combination treatment of the benzamidine derivative and the bisphosphonate compound exhibits excellent inhibitory effect on osteoclast differentiation than the total effect of each individual treatment, thereby being used for the prevention or treatment of osteoporosis.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of priority to U.S. ProvisionalApplication No. 61/085,603, filed Aug. 1, 2008, and U.S. applicationSer. No. 12/363,098, filed Jan. 30, 2009, for which a request to convertto a U.S. Provisional Application was filed on Jul. 31, 2009. Thecontents of these applications are incorporated herein by reference intheir entirety.

TECHNICAL FIELD

The present invention relates to a method of treating or preventingosteoporosis comprising administering to a patient in need thereof aneffective amount of pharmaceutical composition comprising benzamidinederivative or its salt, and bisphosphonate. More particularly, thepresent invention relates to a method of treating or preventingosteoporosis comprising administering to a patient in need thereof aneffective amount of pharmaceutical composition comprising benzamidinederivative or its salt, and bisphosphonate having an improved effectover the pharmaceutical compositions comprising the benzamidine ofFormula 1 or salt thereof, or bisphosphonate, individually.

BACKGROUND ART

Bone is a supporting material for the body's framework and serves toconserve the necessary bone mass and structure. Bone also functions as areservoir of calcium (Ca²⁺) or the like, and plays an important role inmaintaining the calcium level in the blood. To this end, bone undergoescontinuous degradation and remodeling. Thus, bone is in a dynamic steadystate, which maintains a delicate balance by continuously performingboth bone resorption and bone formation. When the balance between boneresorption and bone formation is disrupted, the degree of boneresorption is relatively higher than that of bone formation, which maylead to osteoporosis, a condition which causes reduction in bone densityor bone mass, resulting in decrease in bone strength. This is a diseasewhich frequently occurs in middle-aged or elderly women.

Osteoporosis is a disease, which results from a disturbance in thebalance between bone resorption and bone formation, and is caused byhaving a higher degree of bone resorption relative to that of boneformation. Osteoporosis reduces calcification of bone tissues, anddecreases the level of the compact substances in the bone, whichbroadens the marrow cavity. As osteoporosis progresses, bone becomesbrittle, and bone fracture may easily occur even with a small impact.Bone is a steady state structure, in which the bone formation byosteoblast and the bone resorption by osteoclast occur continuously.

Previous studies on osteoporosis have focused mainly on the metabolismof bone minerals, such as calcium and phosphorus. However, such studiesdid not provide sufficient findings on the mechanisms of osteoporosis.

Bone fracture is associated with an increased mortality rate of patientswith osteoporosis, and also causes serious problems such as negativeimpact on patient's quality of life. Thus, various strategies have beenestablished to produce drugs capable of preventing loss of bone densityand bone fracture.

To date, bisphosphonate (alendronate, etidronate), hormones (raloxifen),vitamin D, calcitonin, calcium agents, or the like have been used as ananti-osteoporotic agent, and Forteo™, a form of parathyroid hormoneresponsible for bone formation, is currently used to treat advancedosteoporosis. However, they are known to have adverse effects.Specifically, hormone agents must be administered throughout patient'slife and in the case of long-term administration, side effects such asbreast cancer, uterus cancer, gallstones and thrombosis may be induced.Vitamin D agents are expensive and show little efficacy, and calcitoninagents are also very expensive and difficult to administer. Calciumagents have few side effects, but their effects are restricted to theprevention of osteoporosis, not the treatment itself. Forteo™, acommercially available parathyroid hormone, has an advantage in that itstimulates bone formation, whereas the known drugs are restricted to theprevention of bone resorption. However, Forteo™ should be given as adaily injection for a long period of time and may increase the risk ofosteosarcoma. Its application is also restricted due to the high price.

A bisphosphonate drug, alendronate or risedronate, represented by thefollowing Formula, has been widely used for the treatment ofosteoporosis and shown to increase bone density and prevent fractures asan inhibitor of bone resorption. Owing to advantages of oraladministration and lower cost, it has been widely used in clinicalfields for the treatment of calcium metabolic disorders includingosteoporosis.

However, bisphosphonate agents show low absorptivity and may induceesophagitis, and thus should be taken with a sufficient amount of waterbefore meals. In addition, patients should wait at least 30 minutesbefore ingesting other beverage or food and avoid lying down for apredetermined time following administration. They are also reported toincrease the risk of hypocalcemia. Recent studies have suggestedproblems such as reduction in bone turnover rate due to excessiveinhibition of bone resorption, inhibition of bone formation,gastrointestinal disorders and osteonecrosis of the jaw. Furthermore, itis recently reported that its long term administration increases therisk of bone fractures (Andrew S Neviaser et al, Journal of OthopaedicTrauma, 2008, 22(5), 346˜350).

As described above, the current therapeutic agents for osteoporosis arenot those which act on both bone resorption and formation. Accordingly,in order to treat osteoporosis, there is a need for the development ofdrugs and therapies which lead to balanced increase in the bone mass andimprovement of bone quality and thus reduce the risk of bone fractures.

To overcome the above drawbacks and improve the clinical efficacy, manystudies have been made, and recent studies suggested combination therapyof a bone resorption inhibitor and a commercially available parathyroidhormone that stimulates bone formation. The detailed description thereofis as follows.

The combination therapy of alendronate and other bone resorptioninhibitor are exemplified by alendronate and estrogen(literature—Lindsay et al, J. Clin. Endocrinol. Metab. 84, 3073-3081(1999)), alendronate and raloxifene (literature—Johnell et al, J. Clin.Endocrinol. Metab. 87, 985-992 (2002)), alendronate and HRT (hormonereplacement therapy) (literature—Greenspan et al, JAMA, 289, 2525-2533(2003)), and alendronate and calcitriol (WO 01/28564). These studiesdemonstrated that the combination therapy showed an increase in bonedensity, compared to their individual administration, but no reductionin the risk of bone fracture. Moreover, problems including reduction inbone turnover rate due to inhibitory effect on bone resorption andinhibition of bone formation still remain, even though there aredifferences between their mechanisms. Thus, there are needs forconsiderations and further studies regarding the therapies.

In this regard, there was a trial of combination therapy with a boneformation stimulator, which was intended to reduce inhibitory effect onbone formation and adverse effects of alendronate. Combination therapyof alendronate with a parathyroid hormone is exemplified by twoliteratures: The effects of parathyroid hormone and alendronate incombination in postmenopausal osteoporosis (literature—Black et al, N.Eng. J. Med. 349, 1207-1215, (2003)) and in elderly men withosteoporosis (literature—Finkelstein et al, N. Eng. J. Med. 349,1216-1226, (2003)). However, the literatures did not demonstrate theincrease in bone density, compared to their individual administration.In this regard, some researchers suggested the possibility that a strongbone resorption inhibitor, alendronate counteracts the stimulatingeffect of parathyroid hormone. Subsequently, a sequential administrationof two drugs has been tried, but further studies are still needed for ameaningful clinical outcome.

The inventors have already disclosed the therapeuric use of thebenzamidine derivatives in osteoporosis in Korea Patent No. 705875,Korea Patent No. 875596, and Korea Patent Application No. 2008-0073710.

The present inventors have also studied the method to increase theprophylactic or therapeutic effect of the benzamidine compounds ofFormula I or salt thereof, by the combined administration with othercompounds, and developed the present compositions with an improvedeffect over the the individual administration that can be used in theprevention and treatment of osteopossis.

[Disclosure] [Technical Problem]

An object of the present inventions is to provide a method of treatingor preventing osteoporosis comprising administering to a patient in needthereof an effective amount of pharmaceutical composition comprisingbenzamidine derivative or its salt, and bisphosphonate.

Another object of the present invention is to provide a method oftreating or preventing osteoporosis comprising administering to apatient in need thereof an effective amount of pharmaceuticalcomposition comprising benzamidine derivative or its salt, andbisphosphonate, with an improved effect when administered together thanadministered individually.

The foregoing and other objects of the present invention can beaccomplished by the following descriptions of the present invention.

[Technical Solution]

In accordance with an aspect, the present invention provides a method oftreating or preventing osteoporosis comprising administering to apatient in need thereof an effective amount of pharmaceuticalcomposition comprising the following compounds (a) and (b) for thepurpose of using simultaneously, separately, or sequentially as activeingredients:

(a) a benzamidine derivative represented by the following Formula 1 orsalt thereof, and

(b) bisphosphonate represented by the following Formula 2,

wherein R₁ is C₁˜C₆ alkyl which is unsubstituted or substituted withpyridinyl; and straight or branched C₁˜C₆ alkyl which is substitutedwith

unsubstituted or substituted with hydroxy; C₃˜C₆ cycloalkyl; phenyl;benzyl; pyridinyl which is unsubstituted or substituted with C₁˜C₆alkyl; guanidino; NR₆R₇; CH₂NR₆R₇; pyridinyl or

group which is substituted with straight or branched C₁˜C₆ alkyl;

(wherein A is C₁˜C₆ alkyl, and m is an integer of 2 to 6); or

group which is unsubstituted or substituted with C₁˜C₆ alkyl,

R₂ is hydrogen; straight or branched C₁˜C₆ alkyl which is unsubstitutedor substituted with NR₈R₉; C₃˜C₆ cycloalkyl; phenyl; benzyl; C₂˜C₆alkenyl; carbonyl which is substituted with NR₈R₉; amino; dimethylamino;morpholinyl; thiomorpholinyl; 4-methylpiperazinyl; or straight orbranched C₁˜C₆ alkyl which is substituted with hydroxy, C₁˜C₆ alkoxy,halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl;

R₃ and R₄ are each independently hydrogen; halogen; hydroxy; C₁˜C₆ alkylwhich is unsubstituted or substituted with halogen; C₃˜C₆cycloalkylamino; C₁˜C₆ alkoxy; C₁˜C₆ alkanoyloxy; C₂˜C₆ alkenyloxy;phenyl-C₁˜C₆ alkoxy; phenoxy; C₂˜C₆ alkenoyloxy or phenyl-C₁˜C₆alkanoyloxy; C₃˜C₆ cycloalkyloxy which is substituted with one groupselected from carboxy, esterified carboxy and amidated carboxy; or anaminooxy group;

R₅ is hydrogen or hydroxy group;

R₆ and R₇ are each independently hydrogen; C₁˜C₆ alkyl which isunsubstituted or substituted with one group selected from hydroxy, C₁˜C₆alkoxy, pyridine and

phenyl; benzyl; pyridinyl; carbonyl which is substituted with one groupselected from C₁˜C6 alkyl, hydroxy, C₁˜C₆ alkoxy, phenyl, benzyl,pyridine and

or C₁˜C₆ alkanesulfonyl;

R₈ and R₉ are each independently hydrogen; C₁˜C₆ alkyl which isunsubstituted or substituted with one group selected from hydroxy, C₁˜C₆alkoxy, morpholine, imidazole and NR₆R₇; C₁˜C₆ alkoxy; C₃˜C₆ cycloalkyl;phenyl; benzyl; pyridinyl; morpholine; carbonyl which is substitutedwith one group selected from C₁˜C₆ alkyl, C₁˜C₆ alkoxy, phenyl, benzyl,pyridine and

carbonyl which is substituted with C₁˜C₆ alkyl substituted with onegroup selected from halogen, C₁˜C₆ alkoxy and imidazole; or C₁˜C₆alkanesulfonyl;

R₁₀ and R₁₁ are each independently hydrogen, C₁˜C₂ alkyl, C₁˜C₃ alkoxyor halide;

X₁ and X₃ are each independently O; S; NH; or N—C₁˜C₆ alkyl, N—C₃˜C₆cycloalkyl, N-benzyl or N-phenyl group;

X₂ is C₃˜C₇ alkylene; C₁˜C₃ alkylene-C₂˜C₇ alkenylene-C₁˜C₃ alkylene;C₁˜C₃ alkylene-O—C₁˜C₃ alkylene; C₁˜C₃ alkylene-S—C₁˜C₃ alkylene; C₁˜C₃alkylene-NH—C₁˜C₃ alkylene; C₁˜C₃ alkylene-phenylene-C₁-C₃ alkylene;C₁-C₃ alkylene-pyridylene-C₁-C₃ alkylene or C₁-C₃alkylene-naphthylene-C₁˜C₃ alkylene; C₃˜C₇ alkylene which is substitutedwith C₁˜C₃ alkyl and hydroxyl; C₃˜C₇ alkylene carbonyl; or C₃˜C₇alkylene which is interrupted by piperazine;

Y is O, S, NR₆ or CH₂ group; and

N is an integer of 0, 1 and 2.

wherein R₁₂ is methyl, chloro, 2-aminoethyl, 3-aminopropyl,4-aminobutyl, 5-aminopentyl, 4-chlorophenylthio, 3-pyridylmethyl,(imidazo[1,2-a]pyridine-3-yl)methyl, 2-(N-methyl-N-n-pentyl)aminoethyl,cycloheptylamino, (1-imidazolyl)methyl or 1-pyrrolidinylethyl group,

R₁₃ is hydrogen, chloro or hydroxy group,

M is hydrogen or sodium, and

Z is any number, preferably an integer of 0 to 7.

In Formula 1, R₁ is particularly methyl, ethyl, isopropyl, cyclohexyl,phenyl, aminomethyl, aminoethyl, amino, pyridinyl, NR₆R₇, CH₂NR₆R₇,

(wherein A is C₁˜C₂ alkyl, and m is an integer of 4 to 5);

R₂ is hydrogen; methyl; ethyl; isopropyl; isobutyl; methoxymethyl;hydroxymethyl; chloromethyl; chloroethyl; cyclopentyl;cyclopentylmethyl; vinyl; methyl or ethyl which is substituted withNR₈R₉; carbonyl which is substituted with NR₈R₉; methyl or ethyl whichis substituted with

methyl or ethyl which is substituted with pyrrolidine, piperidine orimidazole;

piperidine or triazole;

R₃ and R₄ are each independently hydrogen, halogen, hydroxy or methoxygroup;

R₅ is hydrogen or hydroxy group;

R₆ and R₇ are each independently hydrogen, methyl, ethyl, propyl,hydroxyethyl, methoxyethyl, 2-morpholinoethyl, benzyl, pyridine-3-yl,pyridine-4-yl, 2-morpholinoethyl, 4-pyridinylcarbonyl,3-pyridinylcarbonyl, isobutylcarbonyl, ethanesulfonyl, hydroxyethyl, ormethoxyethyl group;

R₈ and R₉ are each independently hydrogen; methyl; ethyl; propyl;isopropyl; butyl; isobutyl; t-butyl; cyclopropyl; cyclohexyl; ethylwhich is substituted with one group selected from hydroxy, methoxy,2-morpholino and NR₆R₇; propyl which is substituted with one groupselected from 3-isopropoxy and 3-imidazole; carbonyl which issubstituted with one group selected from 3-pyridinyl, 4-pyridinyl andisopropyl;

R₁₀ and R₁₁ are each independently hydrogen or methyl; X₁ and X₃ areeach independently oxygen, sulfur, amine or methylamine group;

X₂ is propylene, butylene, pentylene, hexylene, ethylene-O-ethylene,ethylene-NH-ethylene, butylene carbonyl, 2-butenyl,methylene-1,2-phenylene-methylene, methylene-1,3-phenylene-methylene,methylene-1,4-phenylene-methylene or methylene-pyridinyl-methylene; and

n is an integer of 0, 1 and 2.

In the compound of Formula 1 of the present invention, R₃ and R₄ are inthe ortho or meta position relative to —X₁— or —X₃—, and —C(NH₂)═N—R₅ isin the meta or para position.

In one embodiment, the R₁ is C₁˜C₅ alkyl; C₁˜C₅ alkyl substituted withpiperidinyl; C₃˜C₆ cycloalkyl; phenyl; pyridinyl; guanidino; NR₆R₇;piperidinyl or piperazinyl substituted with straight C₁˜C₃ alkyl;morpholinyl; or piperidinyl;

the R₂ is hydrogen; straight or branched C₁˜C₄ alkyl which isunsubstituted or substituted with NR₈R₉; C₃˜C₆ cycloalkyl; benzyl; C₂˜C₆alkenyl; carbonyl which is substituted with NR₈R₉; amino; dimethylamino;morpholinyl; thiomorpholinyl; 4-methylpiperazinyl; or straight orbranched C₁˜C₃ alkyl which is substituted with C₁˜C₃ alkoxy, halogen,C₃˜C₆ cycloalkyl, morpholinyl, dimethylmorpholinyl, thiomorpholinyl,4-methylpiperazinyl, piperidinyl, imidazolyl, or pyrrolidinyl,

the R₃ is hydrogen,

the R₄ is hydrogen, hydroxy or fluoro,

the R₅ is hydrogen or hydroxy;

the R₆ and R₇ are each independently hydrogen; C₁˜C₃ alkyl which isunsubstituted or substituted with one group selected from hydroxy, C₁˜C₃alkoxy, pyridinyl, morpholinyl and piperidinyl; benzyl; carbonyl whichis substituted with one group selected from C₁˜C₃ alkyl, C₁˜C₃ alkylsubstituted with hydroxy and pyridinyl; or C₁˜C₃ alkanesulfonyl;

the R₈ and R₉ are each independently hydrogen; C₁˜C₄ alkyl which isunsubstituted or substituted with one group selected from hydroxy, C₁˜C₃alkoxy, morpholinyl and imidazolyl; C₃˜C₆ cycloalkyl; benzyl; orpyridinoyl; and

the X₁—X₂—X₃ is

In one embodiment, the R₁ is methyl; ethyl; isopropyl; tert-butyl;pentyl; piperidin-1-ylmethyl; cyclohexyl; phenyl; pyridin-3-yl;guanidino; NR₆R₇; 1-propyl-piperidin-4-yl; 4-methyl-piperazin-1-yl;morpholin-4-yl; or piperidin-4-yl;

the R₂ is hydrogen; methyl, ethyl, propyl, isopropyl or butyl which isunsubstituted or substituted with NR₈R₉; cyclopentyl; benzyl; ehthenyl;carbonyl which is substituted with NR₈R₉; amino; dimethylamino;morpholin-4-yl; thiomorpholin-4-yl; 4-methylpiperazin-1-yl; or straightor branched C₁˜C₃ alkyl which is substituted with methoxy, chloro,cyclopentyl, morpholin-4-yl, 2,6-dimethylmorpholin-4-yl,thiomorpholin-4-yl, 4-methylpiperazin-1-yl, piperidin-1-yl,imidazol-1-yl, or pyrrolidin-1-yl;

the R₆ and R₇ are each independently hydrogen; methyl; ethyl; propyl;C₁˜C₃ alkyl which is substituted with one group selected from hydroxy,methoxy, pyridin-3-yl, pyridin-4-yl, morpholin-4-yl and piperidin-1-yl;benzyl; carbonyl which is substituted with one group selected fromisopropyl, hydroxymethyl, pyridin-3-yl and pyridin-4-yl; orethanesulfonyl; and

the R₈ and R₉ are each independently hydrogen; methyl; ethyl; propyl;isopropyl; butyl; isobutyl; tert-butyl; C₁˜C₃ alkyl which is substitutedwith one group selected from hydroxy, methoxy, isopropoxy,morpholin-4-yl and imidazol-1-yl; cyclopropyl; cyclohexyl; benzyl;3-pyridinoyl or 4-pyridinoyl.

In one embodiment, the only one between the R₆ and the R₇ is hydrogen.

In one embodiment, the R₆ and R₇ are both hydrogen; or C₁˜C₆ alkyl whichis unsubstituted or substituted with one group selected from hydroxy,C₁˜C₆ alkoxy and pyridinyl.

Preferably, the R₆ and R₇ are both hydrogen; methyl; methyl substitutedwith pyridinyl; ethyl; ethyl substituted with hydroxy or methoxy; orpropyl.

In one embodiment, the R₆ is methyl; and

the R₇ is C₁˜C₆ alkyl which is unsubstituted or substituted with onegroup selected from hydroxy, C₁˜C₆ alkoxy, pyridinyl and morpholinyl;benzyl; or carbonyl which is substituted with C₁˜C₆ alkyl.

Preferably, the R₇ is methyl which is substituted with pyridin-3-yl orpyridin-4-yl; ethyl which is unsubstituted or substituted with one groupselected from hydroxy, methoxy and morpholin-4-yl; benzyl; carbonylwhich is substituted with isopropyl.

In one embodiment, the R₆ is ethyl; and

the R₇ is C₁˜C₆ alkyl which is unsubstituted or substituted with hydroxyor morpholinyl; or benzyl.

Preferably, the R₇ is ethyl which is substituted with hydroxy ormorpholinyl; or benzyl.

In one embodiment, the only one between the R₈ and the R₉ is hydrogen.

In one embodiment, the R₈ and R₉ are both C₁˜C₆ alkyl which isunsubstituted or substituted with hydroxy.

Preferably, the R₈ and R₉ are both ethyl, hydroxyethyl or propyl.

In one embodiment, the R₈ is C₃˜C₆ cycloalkyl; and

the R₉ is carbonyl substituted with pyridinyl.

Preferably, the R₈ is cyclohexyl;

the R₉ is 3-pyridinoyl or 4-pyridinoyl.

In one embodiment, the R₁ is C₁˜C₆ alkyl which is unsubstituted orsubstituted with pyridinyl; and

the R₂ is hydrogen; straight or branched C₁˜C₆ alkyl which isunsubstituted or substituted with NR₈R₉; C₃˜C₆ cycloalkyl; C₂˜C₆alkenyl; carbonyl which is substituted with NR₈R₉; amino; dimethylamino;morpholinyl; or straight or branched C₁˜C₆ alkyl which is substitutedwith hydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.

In one embodiment, the R₁ is straight or branched C₁˜C₆ alkyl which issubstituted with

unsubstituted or substituted with hydroxyl; and

the R₂ is straight or branched C₁˜C₆ alkyl which is substituted withhydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.

In one embodiment, the R₁ is C₃˜C₆ cycloalkyl; and

the R₂ is hydrogen; straight or branched C₁˜C₆ alkyl which isunsubstituted or substituted with NR₈R₉; or straight or branched C₁˜C₆alkyl which is substituted with hydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆cycloalkyl,

imidazolyl, or pyrrolidinyl.

In one embodiment, the R₁ is phenyl or benzyl; and

the R₂ is phenyl; benzyl; amino; or straight or branched C₁˜C₆ alkylwhich is substituted with hydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆cycloalkyl,

imidazolyl, or pyrrolidinyl.

In one embodiment, the R₁ is pyridinyl which is unsubstituted orsubstituted with C₁˜C₆ alkyl; and

the R₂ is hydrogen; straight or branched C₁˜C₆ alkyl which isunsubstituted or substituted with NR₈R₉; phenyl; benzyl; C₂˜C₆ alkenyl;or straight or branched C₁˜C₆ alkyl which is substituted with hydroxy,C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.

In one embodiment, the R₁ is guanidino; and

the R₂ is straight or branched C₁˜C₆ alkyl which is unsubstituted orsubstituted with NR₈R₉.

In one embodiment, the R₁ is NR₆R₇ or CH₂NR₆R₇; and

the R₂ is hydrogen; straight or branched C₁˜C₆ alkyl which isunsubstituted or substituted with NR₈R₉; C₃˜C₆ cycloalkyl; C₂˜C₆alkenyl; carbonyl which is substituted with NR₈R₉; or straight orbranched C₁˜C₆ alkyl which is substituted with hydroxy, C₁˜C₆ alkoxy,halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.

In one embodiment, the R₁ is

group which is substituted with straight or branched C₁˜C₆ alkyl; and

the R₂ is straight or branched C₁˜C₆ alkyl which is unsubstituted orsubstituted with NR₈R₉; C₃˜C₆ cycloalkyl; morpholinyl; thiomorpholinyl;4-methylpiperazinyl; or straight or branched C₁˜C₆ alkyl which issubstituted with hydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.

Among the benzamidine derivatives of Formula 1 of the present invention,the preferred compounds are as follows:

1)N-hydroxy-4-{5-[4-(2-isopropyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

2)4-{5-[4-(2-isopropyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

3)N-hydroxy-4-{5-[4-(2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

4)N-hydroxy-4-{5-[4-(2-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

5)N-hydroxy-4-{5-[4-(2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

6)N-hydroxy-4-{5-[4-(2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

7)N-hydroxy-4-{5-[4-(2-pyridine-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

8)N-hydroxy-4-{5-[4-(2-cyclohexyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

9)N-hydroxy-4-{5-[4-(2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

10)N-hydroxy-4-{5-[4-(2,5-dimethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

11)N-hydroxy-4-{5-[4-(2-ethyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

12)N-hydroxy-4-{5-[4-(5-methyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

13)N-hydroxy-4-{5-[4-(5-methyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

14)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

15)N-hydroxy-4-{5-[4-(5-methyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

16)N-hydroxy-4-{5-[4-(2-t-butyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

17)N-hydroxy-4-{5-[4-(5-ethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

18)N-hydroxy-4-{5-[4-(2,5-diethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

19)N-hydroxy-4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

20)N-hydroxy-4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

21)N-hydroxy-4-{5-[4-(5-ethyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

22)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

23)N-hydroxy-4-{5-[4-(5-ethyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

24)N-hydroxy-4-{5-[4-(2-ethyl-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

25)N-hydroxy-4-{5-[4-(2,5-diisopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

26)N-hydroxy-4-{5-[4-(5-isopropyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

27)N-hydroxy-4-{5-[4-(5-isopropyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

28)N-hydroxy-4-{5-[4-(5-isopropyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

29)N-hydroxy-4-{5-[4-(2-methyl-5-propyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

30)N-hydroxy-4-{5-[4-(5-butyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

31)N-hydroxy-4-{5-[4-(5-butyl-2-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

32)N-hydroxy-4-{5-[4-(5-butyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

33)N-hydroxy-4-{5-[4-(5-butyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

34)N-hydroxy-4-{5-[4-(5-butyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

35)N-hydroxy-4-{5-[4-(5-butyl-2-cyclohexyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

36)N-hydroxy-4-{5-[4-(5-butyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

37)N-hydroxy-4-{5-[4-(5-butyl-2-t-butyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

38)N-hydroxy-4-{5-[4-(5-benzyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

39)N-hydroxy-4-{5-[4-(5-benzyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

40)N-hydroxy-4-{5-[4-(5-benzyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

41)N-hydroxy-4-{5-[4-(5-benzyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

42)N-hydroxy-4-{5-[4-(5-(2-chloro-ethyl)-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

43)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

44)N-hydroxy-4-{5-[4-(5-isobutyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

45)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

46)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

47)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

48)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

49)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

50)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-cyclohexyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

51)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

52) 4-{5-[4-(2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

53)4-{5-[4-(2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

54)4-{5-[4-(2,5-dimethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

55)4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

56)4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

57)N-hydroxy-4-{5-[4-(2-amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

58)N-hydroxy-4-{5-[4-(2-amino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

59)N-hydroxy-4-{5-[4-(2-guanidino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

60)N-hydroxy-4-{5-[4-(2-amino-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

61)N-hydroxy-4-{5-[4-(2-amino-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

62)N-hydroxy-4-{5-[4-(2-guanidino-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

63)N-hydroxy-4-{5-[4-(2-amino-5-butyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

64)N-hydroxy-4-{5-[4-(5-butyl-2-guanidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

65)N-hydroxy-4-{5-[4-(2-amino-5-benzyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

66)N-hydroxy-4-{5-[4-(5-benzyl-2-guanidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

67)N-hydroxy-4-{5-[4-(2-amino-5-cyclopentylmethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

68)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(1-propyl-piperidin-4-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

69)N-hydroxy-4-{5-[4-(2-(isobutyryl)amino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

70)N-hydroxy-4-{5-[4-(5-isopropyl-2-morpholinomethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

71)N-hydroxy-4-{5-[4-(2-aminomethyl-5-benzyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

72)N-hydroxy-4-{5-[4-(5-methyl-2-(1-propyl-piperidin-4-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

73)N-hydroxy-4-{5-[4-(5-isopropyl-2-aminomethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

74)N-hydroxy-4-{5-[4-(5-vinyl-2-methyl-1,3-thiazole-4-yl)phenoxy]pentyloxy}-benzamidine,

75)N-hydroxy-4-{5-[4-(5-hydroxymethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

76)N-hydroxy-4-{5-[4-(5-methoxymethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

77)N-hydroxy-4-{5-[4-(5-(2-chloroethyl)-2-amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

78)N-hydroxy-4-{5-[4-(5-vinyl-2-amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

79)N-hydroxy-4-{5-[4-(5-vinyl-2-(pyridin-3-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

80)N-hydroxy-4-{5-[4-(5-(2-chloroethyl)-2-(pyridin-3-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

81)N-hydroxy-4-{5-[4-(2-amino-5-cyclopentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

82)N-hydroxy-4-{5-[4-(5-ethyl-2-aminomethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

83)N-hydroxy-4-{5-[4-(5-isopropyl-2-(piperidin-3-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

84)N-hydroxy-4-{5-[4-(2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

85)N-hydroxy-4-{5-[4-(2-ethanesulphonylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

86)N-hydroxy-4-{5-[4-(5-methyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

87)N-hydroxy-4-{5-[4-(2-ethylamino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

88)N-hydroxy-4-{5-[4-(5-methyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

89)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

90)N-hydroxy-4-{5-[4-(2-hydroxyacetylamino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

91)N-hydroxy-4-{5-[4-(5-methyl-2-(4-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

92)N-hydroxy-4-{5-[4-(5-methyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

93)N-hydroxy-4-{5-[4-(2-ethanesulphonylamino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

94)N-hydroxy-4-{5-[4-(2-(2-methoxyethyl)amino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

95)N-hydroxy-4-{5-[4-(2-ethanesulphonylamino-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

96)N-hydroxy-4-{5-[4-(5-ethyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

97)N-hydroxy-4-{5-[4-(5-ethyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

98)N-hydroxy-4-{5-[4-(5-ethyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

99)N-hydroxy-4-{5-[4-(5-ethyl-2-methoxyacetylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

100)N-hydroxy-4-{5-[4-(5-ethyl-2-(4-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

101)N-hydroxy-4-{5-[4-(5-ethyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

102)N-hydroxy-4-{5-[4-(5-ethyl-2-(2-methoxyethyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

103)N-hydroxy-4-{5-[4-(5-isopropyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

104)N-hydroxy-4-{5-[4-(2-ethylamino-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

105)N-hydroxy-4-{5-[4-(5-butyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

106)N-hydroxy-4-{5-[4-(5-butyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

107)N-hydroxy-4-{5-[4-(5-benzyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

108)N-hydroxy-4-{5-[4-(5-benzyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

109)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

110)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

111)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

112)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(4-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

113)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

114)N-hydroxy-4-{5-[4-(5-isopropyl-2-[(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

115)N-hydroxy-4-{5-[4-(5-(2-chloroethyl)-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

116)N-hydroxy-4-{5-[4-(2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

117)N-hydroxy-4-{5-[4-(5-ethyl-2-(pyridin-3-ylmethyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

118)N-hydroxy-4-{5-[4-(2-(ethanesulphonyl-methyl-amino)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

119)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

120)N-hydroxy-4-[5-(4-{2-[(2-hydroxyethyl)-methyl-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

121)N-hydroxy-4-[5-(4-{2-[ethyl-(2-hydroxyethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

122)N-hydroxy-4-[5-(4-{2-[bis-(2-methoxyethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

123)N-hydroxy-4-[5-(4-{5-methyl-2-[methyl-(2-morpholinoethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

124)N-hydroxy-4-[5-(4-{2-[ethyl-1-(2-morpholinoethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

125)N-hydroxy-4-{5-(4-[2-(benzyl-methyl-amino)-5-methyl-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,

126)N-hydroxy-4-[5-{4-[5-methyl-2-(methyl-pyridin-3-yl-methyl-amino)-1,3-thiazol-4-yl]phenoxy}pentyloxy]-benzamidine,

127)N-hydroxy-4-[5-{4-[2-(benzyl-ethyl-amino)-5-methyl-1,3-thiazol-4-yl]phenoxy}pentyloxy]-benzamidine,

128)N-hydroxy-4-[5-(4-{2-[bis-(2-hydroxyethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

129)N-hydroxy-4-[5-(4-{5-ethyl-2-[(2-hydroxyethyl)-methyl-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

130)N-hydroxy-4-[5-(4-{5-ethyl-2-[ethyl-(2-hydroxyethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

131)N-hydroxy-4-[5-(4-{5-ethyl-2-[methyl-(2-morpholinoethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

132)N-hydroxy-4-[5-(4-{5-ethyl-2-[ethyl-(2-morpholinoethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

133)N-hydroxy-4-[5-{4-[2-(benzyl-methyl-amino)-5-ethyl-1,3-thiazol-4-yl]phenoxy}pentyloxy]-benzamidine,

134)N-hydroxy-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

135)N-hydroxy-4-(5-{4-[2-(benzyl-ethyl-amino)-5-ethyl-1,3-thiazol-4-yl]phenoxy}pentyloxy)-benzamidine,

136)N-hydroxy-4-{5-(4-[5-ethyl-2-(ethyl-[pyridin-3-ylmethyl]amino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,

137)N-hydroxy-4-[5-(4-{2-[bis-(pyridin-3-ylmethyl)amino]-5-ethyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

138)N-hydroxy-4-{5-[4-(2-dipropylamino-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

139)N-hydroxy-4-[5-(4-{2-[bis-(2-hydroxyethyl)amino]-5-ethyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

140)N-hydroxy-4-[5-(4-{2-[(2-hydroxyethyl)-methyl-amino]-5-isopropyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

141)N-hydroxy-4-[5-(4-{5-isopropyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

142)N-hydroxy-4-(5-{4-[2-(ethanesulphonyl-methyl-amino)-5-isopropyl-1,3-thiazol-4-yl]phenoxy}pentyloxy)-benzamidine,

143)N-hydroxy-4-[5-(4-{5-butyl-2-[(2-hydroxyethyl)-methyl-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

144)N-hydroxy-4-[5-(4-{5-butyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

145)N-hydroxy-4-[5-(4-{5-butyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

146)N-hydroxy-4-{5-[4-(5-butyl-2-dipropylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

147)N-hydroxy-4-[5-(4-{5-cyclopentylmethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

148)N-hydroxy-4-[5-(4-{5-cyclopentylmethyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

149)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-dipropylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

150)N-hydroxy-4-{5-[4-(5-butyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

151)N-hydroxy-4-{5-[4-(5-butyl-2-ethylmethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

152)N-hydroxy-4-{5-[4-(5-butyl-2-dimethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

153)N-hydroxy-4-[5-(4-{5-cyclopentyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

154)N-hydroxy-4-[5-(4-{5-isobutyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

155)N-hydroxy-4-(5-{4-[5-(2-chloroehtyl)-2-dimethylamino-1,3-thiazol-4-yl]phenoxy}pentyloxy)-benzamidine,

156)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

157)N-hydroxy-4-{5-[4-(5-isopropyl-2-dipropylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

158)N-hydroxy-4-{5-[4-(5-ethyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

159)N-hydroxy-4-[5-(4-{5-isopropyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

160)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

161)N-hydroxy-4-{5-[4-(5-isopropyl-2-dimethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

162)N-hydroxy-4-{5-[4-(5-isopropyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

163)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-dimethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

164)N-hydroxy-4-{5-[4-(5-methyl-2-piperidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

165)N-hydroxy-4-{5-[4-(5-methyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

166)N-hydroxy-4-{5-[4-(5-ethyl-2-piperidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

167)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-piperidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

168)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

169)N-hydroxy-4-{5-[4-(5-isopropyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

170)N-hydroxy-4-{5-(4-[5-cyclopentylmethyl-2-(4-methylpiperazino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,

171)N-hydroxy-4-{5-[4-(5-vinyl-2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

172)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

173)N-hydroxy-4-{5-[4-(5-isobutyl-2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

174)N-hydroxy-4-{5-(4-[5-ethyl-2-(4-methylpiperazino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,

175)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

176)N-hydroxy-4-{5-(4-[5-isopropyl-2-(4-methylpiperazino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,

177)N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentylamino}-benzamidine,

178)N-hydroxy-4-(2-{2-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-ethoxy}-ethoxy)-benzamidine,

179)N-hydroxy-4-{3-hydroxy-5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-3-methyl-pentyloxy}-benzamidine,

180)N-hydroxy-4-(2-{2-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-1-methyl-ethylamino}-ethoxy)-benzamidine,

181)N-hydroxy-4-[3-(4-{3-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-propyl}-piperazine-1-yl)-propoxy]-benzamidine,

182)N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentanoyl-amino}-benzamidine,

183)N-hydroxy-4-({5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyl}-methyl-amino)-benzamidine,

184)N-hydroxy-4-{4-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-but-2-enyloxy}-benzamidine,

185)N-hydroxy-4-{4-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

186)N-hydroxy-4-(2-{2-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)phenoxy]-ethylamino}-ethoxy)-benzamidine,

187)N-hydroxy-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

188)2,N-dihydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

189)N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-3-methoxy-benzamidine,

190)N-hydroxy-2-cyclohexylamino-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

191)N-hydroxy-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

192)N-hydroxy-2-fluoro-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

193)N-hydroxy-4-{3-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)phenoxy]propoxy}-benzamidine,

194)N-hydroxy-4-{4-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)phenoxy]butoxy}-benzamidine,

195)N-hydroxy-3-{5-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxy]-pentylamino}-benzamidine,

196)N-hydroxy-4-{4-[4-(2-cyclohexyl-5-ethyl-thiazol-4-yl)-phenoxy]-butoxy}-benzamidine,

197)N-hydroxy-4-[5-(4-{5-ethyl-2-[(2-hydroxyethyl)-methyl-amino]-thiazol-4-yl}phenoxy)propoxy]-benzamidine,

198)N-hydroxy-4-[5-(4-{5-ethyl-2-[(2-hydroxyethyl)-methyl-amino]-thiazol-4-yl}phenoxy)butoxy]-benzamidine,

199)N-hydroxy-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-thiazol-4-yl}phenoxy)propoxy]-benzamidine,

200)N-hydroxy-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-thiazol-4-yl}phenoxy)butoxy]-benzamidine,

201)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-isopropyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

202)N-hydroxy-4-{4-[4-(5-butyl-2-isopropyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

203)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-amino-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

204)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-amino-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-2-fluoro-benzamidine,

205)N-hydroxy-4-{4-[4-(2-methylamino-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

206)N-hydroxy-4-{6-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxymethyl]-pyridine-2-yl-methoxy}-benzamidine,

207)N-hydroxy-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxy]-butoxy}-benzamidine,

208)N-hydroxy-4-{2-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

209)N-hydroxy-4-{3-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

210)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-cyclohexyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,

211)N-hydroxy-4-{6-[4-(5-isopropyl-2-methyl-thiazol-4-yl)phenoxy]-hexyloxy}-benzamidine,

212)N-hydroxy-4-{5-[2-ethyl-5-hydroxy-4-(2-methyl-thiazol-4-yl)phenoxy]-pentyloxy}-benzamidine,

213)N-hydroxy-4-{5-[2-ethyl-4-(2-methyl-thiazol-4-yl)-5-propoxy-phenoxy]-pentyloxy}-benzamidine,

214)N-hydroxy-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

215)4-(5-{4-[5-(2-isobutylaminoethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

216)N-hydroxy-4-(5-{4-[2-methyl-5-(2-piperidin-1-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

217)N-hydroxy-4-[5-(4-{2-methyl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)--pentyloxy]-benzamidine,

218)N-hydroxy-4-[5-(4-{5-[2-(3-imidazol-1-yl-propylamino)-ethyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

219)N-hydroxy-4-(5-{4-[5-(2-isopropylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

220)N-hydroxy-4-[5-(4-{5-[2-(3-isopropoxy-propylamino)-ethyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

221)N-hydroxy-4-(5-{4-[5-(2-butylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

222)N-hydroxy-4-(5-{4-[5-(2-imidazol-1-yl-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

223)N-hydroxy-4-(5-{4-[5-(2-cyclohexylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

224)N-hydroxy-4-(5-{4-[5-(2-diethylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

225)N-hydroxy-4-{5-[4-(5-{2-[bis-(2-hydroxy-ethyl)-amino]-ethyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

226)N-hydroxy-4-(5-{4-[5-(2-diisopropylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

227)N-hydroxy-4-[5-(4-{5-[2-(2,6-dimethyl-morpholin-4-yl)-ethyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

228)N-hydroxy-4-(5-{4-[2-methyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

229)N-hydroxy-4-(5-{4-[2-amino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

230)N-hydroxy-4-[5-(4-{5-[2-(2-dimethylamino-ethylamino)-ethyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

231)N-hydroxy-4-(5-{4-[2-methyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

232)N-hydroxy-4-[5-(4-{2-methyl-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

233)N-hydroxy-4-{5-[4-(5-{2-[bis-(2-methoxy-ethyl)-amino]-ethyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

234)N-hydroxy-4-(5-{4-[5-(2-tert-butylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

235)N-hydroxy-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

236)N-hydroxy-4-(5-{4-[5-(2-morpholin-4-yl-ethyl)-2-pyridine-3-yl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

237)N-hydroxy-4-[5-(4-{5-[2-(4-methyl-piperazin-1-yl)-ethyl]-2-pyridin-3-yl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

238)N-hydroxy-4-(5-{4-[2-pyridin-3-yl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

239)N-hydroxy-4-(5-{4-[5-(2-imidazol-1-yl-ethyl)-2-pyridin-3-yl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

240)N-hydroxy-4-(5-{4-[2-isopropyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

241)N-hydroxy-4-[5-(4-{2-isopropyl-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

242)N-hydroxy-4-(5-{4-[5-(2-imidazol-1-yl-ethyl)-2-isopropyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

243)N-hydroxy-4-[5-(4-{2-isopropyl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

244)N-hydroxy-4-[5-(4-{5-[2-(3-imidazol-1-yl-propylamino)-ethyl]-2-isopropyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

245)N-hydroxy-4-(5-{4-[2-isopropyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

246)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

247)N-hydroxy-4-[5-(4-{2-cyclohexyl-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

248)N-hydroxy-4-[5-(4-{2-cyclohexyl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

249)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

250)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-dimethylamino-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

251)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-dipropylamino-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

252)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-cyclopropylamino-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

253)N-hydroxy-4-[5-(4-{2-amino-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

254)N-hydroxy-4-(5-{4-[5-(2-morpholin-4-yl-ethyl)-2-phenyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

255)N-hydroxy-4-(5-{4-[2-ethyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

256)N-hydroxy-4-(5-{4-[2-ethyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

257)N-hydroxy-4-(4-{4-[2-methyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-butoxy)-benzamidine,

258)4-(5-{4-[2-cyclohexyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

259)4-(5-{4-[2-methyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

260)N-hydroxy-4-(5-{4-[2-methylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

261)N-hydroxy-4-[5-(4-{2-methylamino-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

262)N-hydroxy-4-(5-{4-[2-methylamino-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

263)N-hydroxy-4-[5-(4-{2-methylamino-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

264)N-hydroxy-4-[5-(4-{5-[2-(3-imidazol-1-yl-propylamino)-ethyl]-2-methylamino-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

265)4-(5-{4-[2-methylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

266)N-hydroxy-4-(5-{4-[2-dimethylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

267)N-hydroxy-4-(5-{4-[2-dimethylamino-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

268)N-hydroxy-4-(5-{4-[2-(isobutyryl-methyl-amino)-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

269)N-hydroxy-4-(5-{4-[2-[benzyl-(2-morpholin-4-yl-ethyl)-amino]-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

270)N-hydroxy-4-(5-{4-[2-diethylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

271)N-hydroxy-4-(5-{4-[2-[bis-(2-methoxy-ethyl)-amino]-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

272)N-hydroxy-4-(5-{4-[2-morpholin-4-yl-5-(2-morpholine-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

273)N-hydroxy-4-(5-{4-[2-morpholin-4-yl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

274)N-hydroxy-4-[5-(4-{5-[2-(4-methyl-piperazin-1-yl)-ethyl]-2-morpholin-4-yl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

275)N-hydroxy-4-[5-(4-{2-morpholin-4-yl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazole-4-yl}-phenoxy)-pentyloxy]-benzamidine,

276)N-hydroxy-4-(5-{4-[5-(2-morpholin-4-yl-ethyl)-2-piperidin-1-yl-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

277)4-(5-{4-[2-morpholin-4-yl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

278)N-hydroxy-4-(5-{4-[5-(2-isobutyrylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

279)N-hydroxy-4-{5-[4-(5-{2-[isobutyl-(pyridin-3-carbonyl)-amino]-ethyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

280)N-hydroxy-4-{5-[4-(5-{2-[cyclopropyl-(pyridin-4-carbonyl)-amino]-ethyl}-2-isopropyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

281)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-{2-[cyclopropyl-(pyridin-3-carbonyl)-amino]-ethyl}-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

282)N-hydroxy-4-{5-[4-(5-methylcarbamoyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

283)N-hydroxy-4-{5-[4-(5-isopropylcarbamoyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

284)N-hydroxy-4-{5-[4-(5-{3-imidazol-1-yl-propylcarbamoyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

285)N-hydroxy-4-{5-[4-(2-amino-5-methylcarbamoyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

286)N-hydroxy-4-{5-[4-(2-methyl-5-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

287)N-hydroxy-4-(5-{4-[2-methyl-5-(4-methyl-piperazin-1-yl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

288)N-hydroxy-4-{5-[4-(2-amino-5-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

289)N-hydroxy-4-(5-{4-[5-(4-methyl-piperazin-1-yl)-2-morpholine-4-yl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

290)N-hydroxy-4-{5-[4-(2,5-di-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

291)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-5-thiomorpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

292)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-5-pyrolidin-1-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

293)N-hydroxy-4-{5-[4-(2-methyl-5-morpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

294)N-hydroxy-4-(5-{4-[2-methyl-5-(4-methyl-piperazin-1-ylmethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

295)N-hydroxy-4-{5-[4-(2-methyl-5-thiomorpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

296)N-hydroxy-4-{5-[4-(2-methyl-5-piperidin-1-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

297)N-hydroxy-4-{5-[4-(5-dimethylaminomethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

298)N-hydroxy-4-{5-[4-(5-butylaminomethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

b 299)N-hydroxy-4-(5-{4-[5-(isobutylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

300)N-hydroxy-4-(5-{4-[5-(tert-butylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

301)N-hydroxy-4-{5-[4-(2-methyl-5-propylaminomethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

302)N-hydroxy-4-[5-(4-{2-methyl-5-[(2-morpholin-4-yl-ethylamino)-methyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

303)N-hydroxy-4-[5-(4-{5-[(3-imidazol-1-yl-propylamino)-methyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

304)N-hydroxy-4-{5-[4-(2-methyl-5-pyrolidin-1-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

305)N-hydroxy-4-{5-[4-(5-imidazol-1-ylmethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

306)N-hydroxy-4-(5-{4-[5-(benzylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

307)N-hydroxy-4-{5-[4-(5-cyclopropylaminomethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,p 308)N-hydroxy-4-{5-[4-(2-methylamino-5-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

309)N-hydroxy-4-(5-{4-[2-(methyl-pyridin-4-ylmethyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

310)N-hydroxy-4-[5-(4-{2-[(2-hydroxy-ethyl)-methyl-amino]-5-morpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

311)N-hydroxy-4-(5-{4-[2-(ethyl-methyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

312)N-hydroxy-4-(5-{4-[2-(benzyl-methyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

313)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-5-morpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

314)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-5-thiomorpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

315)N-hydroxy-4-[5-(4-{5-{[bis-(2-methoxy-ethyl)-amino]-methyl}-2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

316)N-hydroxy-4-(5-{4-[2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-5-(4-methyl-piperazin-1-ylmethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

317)N-hydroxy-4-[5-(4-{5-(isopropylamino-methyl)-2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

318)N-hydroxy-4-[5-(4-{5-[(2-methoxy-ethylamino)-methyl]-2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

319)N-hydroxy-4-[5-(4-{2-[(2-methoxy-ethyl)-methyl-amino]-5-morpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

320)N-hydroxy-4-(5-{4-[2-(methyl-propyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

321)N-hydroxy-4-(5-{4-[2-(methyl-pyridin-3-ylmethyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

322)N-hydroxy-4-{5-[4-(2-methyl-5-methylamino-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

323)N-hydroxy-4-[5-(4-{2-methyl-5-[(pyridin-4-carbonyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

324)N-hydroxy-4-[5-(4-{2-methyl-5-[(pyridin-3-carbonyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

325)N-hydroxy-4-[5-(4-{2-phenyl-5-[(pyridin-3-carbonyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

326)N-hydroxy-4-{5-[4-(5-dimethylamino-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

327)N-hydroxy-4-{5-[4-(5-dimethylamino-2-phenyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

328)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-dimethylamino-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

329)N-hydroxy-4-{5-[4-(2-methyl-5-[1,2,4]triazol-1-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

330)N-hydroxy-4-{5-[4-(5-amino-2-phenyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

331)N-hydroxy-4-{5-[4-(5-amino-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

332)N-hydroxy-4-{5-[4-(5-amino-2-pyridin-3-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

333)N-hydroxy-4-{5-[4-(5-amino-2-ethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

334)N-hydroxy-4-{5-[4-(5-amino-2-cyclohexyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

335)N-hydroxy-4-{5-[4-(2-methylamino-5-morpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

336)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-5-morpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,and

337)N-hydroxy-4-{5-[4-(5-morpholin-4-yl-2-piperidin-1-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine.

Among the benzamidine derivatives of Formula 1 of the present invention,the more preferred compounds are as follows:

1)4-{5-[4-(2,5-dimethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

2)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(1-propyl-piperidin-4-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

3)N-hydroxy-4-{5-[4-(5-vinyl-2-(pyridin-3-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

4)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

5)N-hydroxy-4-{5-[4-(2-(2-methoxyethyl)amino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

6)N-hydroxy-4-{5-[4-(5-ethyl-2-(4-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

7)N-hydroxy-4-{5-[4-(5-ethyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

8)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

9)N-hydroxy-4-[5-{4-[5-methyl-2-(methyl-pyridin-3-yl-methyl-amino)-1,3-thiazol-4-yl]phenoxy}pentyloxy]-benzamidine,

10)N-hydroxy-4-{5-[4-(2-dipropylamino-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

11)N-hydroxy-4-[5-(4-{5-cyclopentylmethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,

12)N-hydroxy-4-{5-[4-(5-methyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

13)N-hydroxy-4-{5-[4-(5-ethyl-2-piperidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

14)N-hydroxy-4-{5-[4-(5-isopropyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,

15)N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentylamino}-benzamidine,

16)N-hydroxy-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

17)N-hydroxy-4-(5-{4-[5-(2-imidazol-1-yl-ethyl)-2-isopropyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

18)N-hydroxy-4-[5-(4-{5-[2-(3-imidazol-1-yl-propylamino)-ethyl]-2-isopropyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,

19)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-dipropylamino-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

20)N-hydroxy-4-(5-{4-[2-ethyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

21)N-hydroxy-4-(5-{4-[2-[benzyl-(2-morpholin-4-yl-ethyl)-amino]-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

22)N-hydroxy-4-(5-{4-[2-diethylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

23)N-hydroxy-4-(5-{4-[2-morpholin-4-yl-5-(2-thiomorpholin-3-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

24)N-hydroxy-4-{5-[4-(2,5-di-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

25)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-5-thiomorpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

26)N-hydroxy-4-{5-[4-(2-methyl-5-piperidin-1-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

27)N-hydroxy-4-(5-{4-[5-(isobutylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

28)N-hydroxy-4-{5-[4-(2-methyl-5-propylaminomethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,

29)N-hydroxy-4-(5-{4-[5-(benzylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

30)N-hydroxy-4-(5-{4-[2-(methyl-pyridin-4-ylmethyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,

31)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-5-thiomorpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,and

32)N-hydroxy-4-{5-[4-(5-amino-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine.

Among the bisphosphonate compounds of Formula 2 of the presentinvention, the preferred compounds are as follows:

1) etidronic acid,

2) clodronic acid,

3) pamidronic acid,

4) tiludronic acid,

5) risedronic acid,

6) minodronic acid,

7) ibandronic acid,

8) zoledronic acid, and

9) alendronic acid.

The benzamidine derivatives of Formula 1 of the present invention may beused in the form of pharmaceutically acceptable salts. Preferable areacid addition salts prepared with pharmaceutically acceptable freeacids. Free acids suitable for use in the present invention may beinorganic acids or organic acids. Examples of the inorganic acids mayinclude hydrochloric acid, bromic acid, sulfuric acid, and phosphoricacid, and the organic acids may be exemplified by citric acid, aceticacid, lactic acid, tartaric acid, fumaric acid, formic acid, propionicacid, oxalic acid, trifluoroacetic acid, methane sulfonic acid, benzenesulfonic acid, maleic acid, benzoic acid, gluconic acid, glycolic acid,succinic acid, 4-morpholine ethane sulfonic acid, camphorsulfonic acid,4-nitrobenzene sulfonic acid, hydroxy-O-sulfonic acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, andaspartic acid. Preferably, hydrochloric acid or phosphoric acid as theinorganic acid and methane sulfonic acid as the organic acid may beused.

In the present invention, general definitions of the substituents of thecompounds of Formulae 1 and 2 have the following meanings:

The term “halogen” means halogen group atoms including chlorine,fluorine, bromine, and iodine radicals.

The term “alkyl” means straight or branched, saturated hydrocarbonradicals having 1 to 6 carbon atoms, and examples thereof includemethyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl and tert-butyl.

The term “alkoxy” means radicals having straight or branched alkylhaving 1 to 6 carbon atoms that is linked to oxygen, and examplesthereof include methoxy, ethoxy, propoxy, iso-propoxy, butoxy,sec-butoxy, and tert-butoxy.

The term “cycloalkyl” means a non-aromatic hydrocarbon ring having 3 to6 carbon atoms, and examples thereof include cyclopropyl, cyclobutyl,cyclopentyl and cyclohexyl.

The term “alkenyl” means straight or branched, unsaturated hydrocarbonshaving 2 to 6 carbon atoms with one or more double bonds.

The term “alkanoyloxy” means an oxygen-containing radical in which aterminal carbon atom of an alkyl group is substituted with a carbonylradical.

The term “alkenoyloxy” means an oxygen-containing radical in which aterminal carbon atom of an alkenyl group is substituted with a carbonylradical.

The term “alkenyloxy” means an oxygen-containing alkenyl group.

The term “alkylene” means a straight or branched, saturated hydrocarbonradical having 1 to 7 carbon atoms, and 2 or more junction centers for acovalent bond, and examples thereof include methylene, ethylene,methylethylene and isopropylidene.

The term “alkenylene” means a straight or branched, unsaturatedhydrocarbon radical having 2 to 7 carbon atoms, 2 or more conjunctioncenters for a covalent bond and one or more double bonds, and examplesthereof include 1,1-vinylidene (CH₂═C), 1,2-vinylidene (—CH═CH—), and1,4-butadienyl (—CH═CH—CH═CH—).

The term “carbonyl” means a carbon radical in which 2 of 4 covalentbonds are linked to oxygen atoms.

The benzamidine of Formula 1 or salts thereof used in the presentinvention can be used as a therapeutic or prophylactic agent forosteoporosis, having excellent inhibitory effect on bone resorption andstimulating effect on bone formation.

The benzamidine derivative of Formula 1 may be prepared by knownprocesses, which are disclosed in Korea Patent No. 705875, and KoreaPatent No. 875596, and Korea Patent Application No. 2008-0073710.

The term “osteoporosis” as used herein means the state that minerals andsubstrates forming the bone are reduced abnormally in large amounts,even without any defect in the structure of the remaining bone, so thatmany pores are generated in the bone, making it like sponge and morelikely to fracture. This may be referred to as “osteopenia”.

The dosage of benzamidine derivative of Formula 1 or salt thereof mayvary depending on patient's body weight, age, gender, health state,diet, administration time period, administration route, excretion rate,disease severity, type of combination therapy, or treatment frequency.In the case of using as a therapeutic or prophylactic agent, thebenzamidine derivative of Formula 1 or salt thereof may be generallyadministered in an effective amount for the treatment of osteoporosisvia each administration route, and its formulation, dosage or the likemay be easily determined by those skilled in the art, consideringadministration purpose, route, health state and body weight of asubject. In particular, the benzamidine derivative or salt thereof maybe administered in a daily dose of about 1 to 1,000 mg, and preferably 5to 400 mg.

In addition, the dosage of bisphosphonate of Formula 2 may varydepending on patient's body weight, age, gender, health state, diet,administration time period, administration route, excretion rate,disease severity, type of combination therapy, or treatment frequency.In the case of using as a therapeutic or prophylactic agent, thebisphosphonate of Formula 2 may be generally administered in aneffective amount for the treatment of osteoporosis via eachadministration route and its formulation, dosage or the like may beeasily determined by those skilled in the art, consideringadministration purpose, route, and health state and body weight of asubject. In particular, the bisphosphonate may be administered in adaily dose of about 1 to 1,000 mg, and preferably 1 to 400 mg.

In the present invention, the benzamidine of Formula 1 or salt thereofand bisphosphonate of Formula 2 may be used in any combination thereof.

In the present invention, the benzamidine of Formula 1 or salt thereofand bisphosphonate of Formula 2 may be simultaneously administered bymixing together, or each of them may be administered separately eithersimultaneously or sequentially, or may be administered separately atdifferent times. In the case of administering separately, two activeingredients may be administered alternately or one active ingredient maybe administered after completion of the administration of the otheractive ingredient.

In the present invention, the benzamidine of Formula 1 or salt thereofand bisphosphonate of Formula 2 may be formulated into anypharmaceutical dosage form, for example, a combined formulationcomprising two active ingredients or each single formulation. As usedherein, the combined formulation means that two active ingredients ofthe benzamidine of Formula 1 or salt thereof and bisphosphonate ofFormula 2 are blended in one formulation, and the single formulationmeans that one active ingredient is contained in one formulation. In thepresent invention, if two active ingredients are prepared into singleformulations, the therapeutic and prophylactic agent of the presentinvention refers to a drug using the single formulations in combinationthereof. Thus, each drug containing the active ingredient may beprepared into each different formulation. If two active ingredients areprepared into single formulation, two formulations may be provided inone kit.

In addition, the prophylactic or therapeutic agent for osteoporosis ofthe present invention may be administered, either daily orintermittently, and may be administered once or 2˜3 times a day. If eachof the active ingredients is a single formulation, their administrationfrequency may be the same as or different from each other.

The benzamidine of Formula 1 or salt thereof and bisphosphonate ofFormula 2 of the present invention may be formulated alone or along withthe following suitable excipients by a known method. Specific examplesof the formulation may include oral dosage forms such as soft capsule,hard capsule, tablet, and syrup, and injectable and topicalpreparations.

As the excipient, the pharmaceutically acceptable carrier includes anyof standard pharmaceutical carriers used for the preparation of theknown formulations, such as sterile liquids, tablets, coated tablets andcapsules. Typically, such carriers include excipients such aspolyvinylpyrrolidone, dextrin, starch, milk, sugar, certain types ofclay, gelatin, stearic acid, talc, vegetable oils (e.g., edible oil,cotton seed oil, coconut oil, almond oil, peanut oil), liquid ester suchas triglyceride, mineral oil, Vaseline, animal fat, cellulosederivatives (e.g., crystalline cellulose, hydroxypropylcellulose,hydroxypropylmethylcellulose, methylcellulose) and other knownexcipients. Such carriers may also include antioxidants, wetting agents,viscosity stabilizers, flavoring agents, coloring additives and otheradditives. The composition containing these carriers may be formulatedby a known method.

The prophylactic or therapeutic composition for osteoporosis of thepresent invention means that two types of active ingredients having adifferent mechanism from each other, including the benzamidine ofFormula 1 or salt thereof and bisphosphonate of Formula 2, are used incombination, and provides excellent effects of improving bone densityand strength, compared to other single drugs.

For the prevention and treatment of osteoporosis, the prophylactic ortherapeutic composition of the present invention may be used alone or incombination with surgical operations, hormone therapies, chemicaltherapies, and other methods using biological reaction regulators.

[Best Mode]

Hereinafter, the present invention will be described in more detail withreference to examples. However, these examples are for illustrativepurposes only, and the invention is not intended to be limited by theseexamples.

PREPARATION EXAMPLE 1 Preparation of Benzamidine Derivative of Formula 1

Benzamidine derivatives of Formula 1 were prepared according to thepreparation methods disclosed in Korea Patent No. 705875, Korea PatentNo. 875596, and Korea Patent Application No. 2008-0073710, thedisclosure of which is incorporated herein by reference in its entirety.

Prepared compounds were identified as following Table 1.

TABLE 1 No. Chemical name NMR data Sol. 1 N-hydroxy-4-{5-[4-(2- 1.31 (d,6H), 1.58 (m, 2H), 1.79 (m, 4H), DMSO-d₆ isopropyl-5-methyl-1,3- 2.47(s, 3H), 3.21 (m, 1H), 4.00 (m, 4H), thiazol-4- 5.71 (s, 2H), 6.91 (d,2H), 6.99 (d, 2H), yl)phenoxy]pentyloxy}- 7.56 (m, 4H), 9.44 (s, 1H)benzamidine 2 4-{5-[4-(2-isopropyl-5- 1.33 (d, 6H), 1.61 (m, 2H), 1.82(brm, DMSO-d₆ methyl-1,3-thiazol-4- 4H), 2.49 (s, 3H), 3.22 (m, 1H),4.04 (t, yl)phenoxy]pentyloxy}- 2H), 4.14 (t, 2H), 7.01 (d, 2H), 7.17(d, benzamidine 2H), 7.57 (d, 2H), 7.85 (d, 2H). 3 N-hydroxy-4-{5-[4-(2-1.56 (m, 2H), 1.78 (brm, 4H), 2.68 (s, DMSO-d₆ methyl-1,3-thiazol-4-3H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, yl)phenoxy]pentyloxy}- 2H),6.96 (d, 2H), 7.57 (d, 2H), 7.72 (s, benzamidine 1H), 7.83 (d, 2H), 9.43(s, 1H) 4 N-hydroxy-4-{5-[4-(2- 1.32 (t, 3H), 1.57 (brm, 2H), 1.77 (brm,DMSO-d₆ ethyl-1,3-thiazol-4- 4H), 3.01 (q, 2H), 4.00 (m, 4H), 5.71 (s,yl)phenoxy]pentyloxy}- 2H), 6.91 (d, 2H), 6.96 (d, 2H), 7.57 (d,benzamidine 2H), 7.75 (s, 1H), 7.84 (d, 2H), 9.43 (s, 1H) 5N-hydroxy-4-{5-[4-(2- 1.35 (d, 6H), 1.58 (m, 2H), 1.78 (brm, DMSO-d₆isopropyl-1,3-thiazol- 4H), 3.28 (m, 1H), 4.00 (m, 4H), 4- 5.79 (brs,2H), 6.91 (d, 2H), 6.97 (d, yl)phenoxy]pentyloxy}- 2H), 7.58 (d, 2H),7.76 (s, 1H), 7.84 (d, benzamidine 2H), 9.47 (s, 1H) 6N-hydroxy-4-{5-[4-(2- 1.58 (m, 2H), 1.80 (brm, 4H), 4.02 (m, DMSO-d₆phenyl-1,3-thiazol-4- 4H), 5.81 (brs, 2H), 6.92 (d, 2H),yl)phenoxy]pentyloxy}- 7.01 (d, 2H), 7.51 (m, 3H), 7.58 (d, 2H),benzamidine 7.96 (d, 2H), 8.01 (m, 3H), 9.49 (s, 1H) 7N-hydroxy-4-{5-[4-(2- 1.58 (brm 2H), 1.80 (brm, 4H), 4.02 (t, DMSO-d₆pyridine-3-yl-1,3- 4H), 5.73 (s, 2H), 6.91 (d, 2H), 7.02 (d, thiazol-4-2H), 7.55 (m, 3H), 7.82 (d, 2H), 7.97 (d, yl)phenoxy]pentyloxy}- 2H),8.10 (s, 1H), 8.36 (d, 1H), 8.67 (d, benzamidine 1H), 9.19 (s, 1H), 9.45(s, 1H) 8 N-hydroxy-4-{5-[4-(2- 1.23 (m, 1H), 1.47 (m, 6H), 1.65 (m,1H), DMSO-d₆ cyclohexyl-1,3-thiazol- 1.77 (brm, 6H), 2.06 (m, 2H), 2.99(m, 4- 1H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, yl)phenoxy]pentyloxy}-2H), 6.96 (d, 2H), 7.57 (d, 2H), 7.74 (d, benzamidine 2H), 7.83 (d, 2H),9.44 (s, 1H) 9 N-hydroxy-4-{5-[4-(2- 0.86 (t, 3H), 1.33 (brm, 4H), 1.56(brm, DMSO-d₆ pentyl-1,3-thiazol-4- 2H), 1.73 (brm, 6H), 2.97 (m, 2H),yl)phenoxy]pentyloxy}- 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H),benzamidine 6.96 (m, 2H), 7.57 (d, 2H), 7.74 (s, 1H), 7.83 (d, 2H), 9.44(s, 1H) 10 N-hydroxy-4-{5-[4-(2,5- 1.57 (m, 2H), 1.78 (m, 4H), 2.44 (s,3H), DMSO-d₆ dimethyl-1,3-thiazol-4- 2.58 (s, 3H), 4.01 (m, 4H), 5.72(s, 2H), yl)phenoxy]pentyloxy}- 6.97 (d, 2H), 7.54 (d, 2H), 7.57 (d,2H), benzamidine 9.44 (s, 1H) 11 N-hydroxy-4-{5-[4-(2- 1.27 (t, 3H),1.57 (m, 2H), 1.78 (brm, DMSO-d₆ ethyl-5-methyl-1,3- 4H), 2.45 (s, 3H),2.91 (q, 2H), 4.01 (m, thiazol-4- 4H), 5.75 (brs, 2H), 6.91 (d, 2H),yl)phenoxy]pentyloxy}- 6.98 (d, 2H), 7.54 (d, 2H), 7.57 (d, 2H),benzamidine 9.46 (s, 1H). 12 N-hydroxy-4-{5-[4-(5- 1.58 (m, 2H), 1.79(m, 4H), 2.56 (s, 3H), DMSO-d₆ methyl-2-phenyl-1,3- 4.02 (m, 4H), 5.78(brs, 2H), 6.91 (d, thiazol-4- 2H), 7.03 (d, 2H). 7.49 (m, 3H), 7.58 (d,yl)phenoxy]pentyloxy}- 2H), 7.65 (d, 2H), 7.91 (d, 2H), 9.45 (s,benzamidine 1H) 13 N-hydroxy-4-{5-[4-(5- 1.59 (m, 2H), 1.79 (m, 2H),2.58 (s, 3H), DMSO-d₆ methyl-2-pyridin-3-yl- 4.02 (m, 4H), 5.72 (s, 2H),6.91 (d, 2H), 1,3-thiazol-4- 7.03 (d, 2H), 7.52 (m, 1H), 7.58 (d, 2H),yl)phenoxy]pentyloxy}- 7.66 (d, 2H), 8.26 (d, 1H), 8.64 (d, 1H),benzamidine 9.09 (d, 1H), 9.45 (s, 1H) 14 N-hydroxy-4-{5-[4-(2- 1.26 (m,1H), 1.43 (brm, 4H), 1.61 (m, DMSO-d₆ cyclohexyl-5-methyl- 2H), 1.67 (m,1H), 1.80 (brm, 6H), 1,3-thiazol-4- 2.04 (m, 1H), 2.49 (s, 3H), 2.92 (m,1H), yl)phenoxy]pentyloxy}- 4.03 (m, 4H), 5.73 (s, 2H), 6.94 (d, 2H),benzamidine 7.01 (d, 2H), 7.57 (d, 2H), 7.60 (d, 2H), 9.47 (s, 1H) 15N-hydroxy-4-{5-[4-(5- 0.86 (t, 3H), 1.31 (brm, 4H), 1.58 (m, DMSO-d₆methyl-2-pentyl-1,3- 2H), 1.68 (m, 2H), 1.78 (brm, 4H), thiazol-4- 2.46(s, 3H), 2.88 (t, 2H), 4.01 (m, 4H), yl)phenoxy]pentyloxy}- 5.72 (brs,2H), 6.92 (d, 2H), 6.98 (d, benzamidine 2H), 7.53 (d, 2H), 7.57 (d, 2H),9.45 (s, 1H) 16 N-hydroxy-4-{5-[4-(2-t- 1.36 (s, 9H), 1.57 (m, 2H), 1.78(brm, DMSO-d₆ butyl-5-methyl-1,3- 4H), 2.45 (s, 3H), 4.00 (m, 4H), 5.72(s, thiazol-4- 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.55 (d,yl)phenoxy]pentyloxy}- 2H), 7.58 (d, 2H), 9.44 (s, 1H) benzamidine 17N-hydroxy-4-{5-[4-(5- 1.26 (t, 3H), 1.66 (m, 2H), 1.85 (brm, CDCl₃ethyl-2-methyl-1,3- 4H), 2.83 (s, 3H), 2.86 (q, 2H), 4.00 (m, thiazol-4-4H), 4.88 (brs, 1H), 6.87 (d, 2H), yl)phenoxy]pentyloxy}- 6.91 (d, 2H),7.46 (d, 2H), 7.52 (d, 2H) benzamidine 18 N-hydroxy-4-{5-[4-(2,5- 1..22(t, 3H), 1.28 (t, 3H), 1.57 (m, DMSO-d₆ diethyl-1,3-thiazol-4- 2H), 1.78(brm, 4H), 2.85 (q, 2H), yl)phenoxy]pentyloxy}- 4.01 (m, 2H), 5.73 (s,2H), 6.91 (d, 2H), benzamidine 6.98 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H),9.44 (s, 1H) 19 N-hydroxy-4-{5-[4-(5- 1.22 (t, 3H), 1.31 (d, 6H), 1.57(m, 2H), DMSO-d₆ ethyl-2-isopropyl-1,3- 1.78 (brm, 4H), 2.86 (q, 2H),3.24 (m, thiazol-4- 1H), 4.01 (m, 4H), 5.70 (s, 2H), 6.90 (d,yl)phenoxy]pentyloxy}- 2H), 6.98 (d, 2H), 7.49 (d, 2H), 7.58 (d,benzamidine 2H), 9.43 (s, 1H) 20 N-hydroxy-4-{5-[4-(5- 1.29 (t, 2H),1.58 (m, 2H), 1.79 (m, 4H), DMSO-d₆ ethyl-2-phenyl-1,3- 2.96 (q, 2H),4.03 (m, 4H), 5.70 (s, 2H), thiazol-4- 6.91 (d, 2H), 7.03 (d, 2H), 7.43(m, 3H), yl)phenoxy]pentyloxy}- 7.58 (m, 4H), 7.90 (m, 2H), 9.43 (s, 1H)benzamidine 21 N-hydroxy-4-{5-[4-(5- 1.30 (t, 3H), 1.58 (m, 2H), 1.79(m, 4H), DMSO-d₆ ethyl-2-pyridin-3-yl- 2.98 (q, 2H), 4.02 (m, 4H), 5.69(s, 2H), 1,3-thiazol-4- 6.91 (d, 2H), 7.04 (d, 2H), 7.52 (m, 1H),yl)phenoxy]pentyloxy}- 7.59 (m, 4H), 8.26 (m, 1H), 8.63 (m, 1H),benzamidine 9.10 (s, 1H), 9.42 (s, 1H) 22 N-hydroxy-4-{5-[4-(2- 1.22 (m,4H), 1.38 (m, 4H), 1.58 (m, 2H), DMSO-d₆ cyclohexyl-5-ethyl-1,3- 1.64(m, 1H), 1.89 (brm, 6H), 2.01 (m, thiazol-4- 2H), 2.87 (m, 3H), 4.01 (m,4H), 5.71 (s, yl)phenoxy]pentyloxy}- 2H), 6.91 (s, 2H), 6.98 (d, 2H),7.48 (d, benzamidine 2H), 7.57 (d, 2H), 9.44 (s, 1H) 23N-hydroxy-4-{5-[4-(5- 0.86 (t, 3H), 1.21 (t, 3H), 1.32 (brm, DMSO-d₆ethyl-2-pentyl-1,3- 4H), 1.58 (m, 2H), 1.69 (m, 2H), thiazol-4- 1.78(brm, 4H), 2.87 (m, 4H), 4.01 (m, yl)phenoxy]pentyloxy}- 4H), 5.72 (s,2H), 6.91 (d, 2H), 6.98 (d, benzamidine 2H), 7.48 (d, 2H), 7.58 (d, 2H),9.44 (s, 1H) 24 N-hydroxy-4-{5-[4-(2- 1.26 (m, 9H), 1.57 (m, 2H), 1.79(brm, DMSO-d₆ ethyl-5-isopropyl-1,3- 4H), 2.92 (q, 2H), 3.31 (m, 1H),4.01 (m, thiazol-4- 4H), 5.71 (brs, 2H), 6.91 (d, 2H),yl)phenoxy]pentyloxy}- 6.98 (d, 2H), 7.43 (d, 2H), 7.57 (d, 2H)benzamidine 25 N-hydroxy-4-{5-[4-(2,5- 1.24 (d, 6H), 1.32 (d, 6H), 1.56(brm, DMSO-d₆ diisopropyl-1,3- 2H), 1.76 (brm, 4H), 3.22-3.27 (m, 1H),thiazol-4- 3.34-3.38 (m, 1H), 3.90 (t, 2H), 4.02 (t,yl)phenoxy]pentyloxy}- 2H), 5.70 (s, 2H), 6.80 (d, 2H), 7.00 (d,benzamidine 2H), 7.26 (d, 2H), 7.45 (d, 2H), 8.29 (s, 1H) 26N-hydroxy-4-{5-[4-(5- 1.31 (d, 6H), 1.58 (brm, 2H), 1.78 (brm, DMSO-d₆isopropyl-2-phenyl-1,3- 4H), 3.44 (m, 1H), 4.02 (m, 4H), 5.70 (s,thiazol-4- 2H), 6.91 (d, 2H), 7.03 (d, 2H), 7.47 (m,yl)phenoxy]pentyloxy}- 3H), 7.56 (m, 4H), 7.90 (d, 2H), 9.44 (s,benzamidine 1H) 27 N-hydroxy-4-{5-[4-(5- 1.32 (d, 6H), 1.57 (brm, 2H),1.78 (brm, DMSO-d₆ isopropyl-2-pyridin-3- 4H), 4.00 (m, 4H), 5.71 (s,2H), 6.91 (d, yl-1,3-thiazol-4- 2H), 7.04 (d, 2H), 7.51 (m, 1H), 7.58(m, yl)phenoxy]pentyloxy}- 4H), 8.27 (d, 1H), 8.64 (d, 1H), 9.10 (d,benzamidine 1H), 9.44 (s, 1H) 28 N-hydroxy-4-{5-[4-(5- 0.84 (t, 3H),1.23 (d, 6H), 1.32 (brm, DMSO-d₆ isopropyl-2-pentyl-1,3- 4H), 1.56 (m,2H), 1.69 (m, 2H), thiazol-4- 1.78 (brm, 4H), 2.88 (m, 2H), 3.36 (m,yl)phenoxy]pentyloxy}- 1H), 4.01 (m, 4H), 5.73 (s, 2H), 6.91 (d,benzamidine 2H), 6.98 (d, 2H), 7.43 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H)29 N-hydroxy-4-{5-[4-(2- 0.91 (t, 3H), 1.57~1.61 (m, 4H), 1.78 (m,DMSO-d₆ methyl-5-propyl-1,3- 4H), 2.60 (s, 3H), 2.80 (m, 2H), 4.01 (m,thiazol-4- 4H), 5.85 (brs, 2H), 6.93 (d, 2H), yl)phenoxy]pentyloxy}-6.98 (d, 2H), 7.47 (d, 2H), 7.58 (d, 2H), benzamidine 9.51 (s, 1H) 30N-hydroxy-4-{5-[4-(5- 0.83 (t, 3H), 1.30 (m, 2H), 1.53 (m, 4H), DMSO-d₆butyl-2-methyl-1,3- 1.78 (brm, 4H), 2.59 (s, 3H), 2.82 (m, thiazol-4-2H), 4.00 (m, 4H), 5.74 (brs, 2H), yl)phenoxy]pentyloxy}- 6.91 (d, 2H),7.46 (d, 2H), 7.57 (d, 2H), benzamidine 9.45 (s, 1H) 31N-hydroxy-4-{5-[4-(5- 0.84 (t, 3H), 1.27 (t, 3H), 1.31 (m, 2H), DMSO-d₆butyl-2-ethyl-1,3- 1.56 (m, 4H), 1.78 (brm, 4H), 2.83 (t, thiazol-4-2H), 2.92 (m, 2H), 4.01 (m, 4H), yl)phenoxy]pentyloxy}- 5.72 (brs, 2H),6.91 (d, 2H), 6.98 (d, benzamidine 2H), 7.47 (d, 2H), 7.58 (d, 2H), 9.45(s, 2H) 32 N-hydroxy-4-{5-[4-(5- 0.84 (t, 3H), 1.31 (m, 8H), 1.57 (m,4H), DMSO-d₆ butyl-2-isopropyl-1,3- 1.78 (brm, 4H), 2.83 (m, 2H), 3.24(m, thiazol-4- 1H), 4.01 (m, 4H), 5.74 (brs, 2H), yl)phenoxy]pentyloxy}-6.91 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), benzamidine 7.57 (d, 2H), 9.45(s, 1H) 33 N-hydroxy-4-{5-[4-(5- 0.86 (t, 3H), 1.33 (m, 2H), 1.61 (m,4H), DMSO-d₆ butyl-2-phenyl-1,3- 1.80 (m, 4H), 2.92 (t, 2H), 4.01 (m,4H), thiazol-4- 5.72 (brs, 2H), 6.91 (d, 2H), 7.02 (d,yl)phenoxy]pentyloxy}- 2H), 7.46 (m, 3H), 7.59 (m, 4H), 7.91 (d,benzamidine 2H), 9.45 (s, 1H) 34 N-hydroxy-4-{5-[4-(5- 0.86 (t, 3H),1.35 (m, 2H), 1.59 (m, 2H), DMSO-d₆ butyl-2-pyridin-3-yl- 1.66 (m, 2H),1.78 (m, 4H), 2.95 (t, 2H), 1,3-thiazol-4- 4.03 (m, 4H), 5.75 (brs, 2H),6.91 (d, yl)phenoxy]pentyloxy}- 2H), 7.04 (d, 2H), 7.51 (m, 1H), 7.58(m, benzamidine 4H), 8.26 (d, 1H), 8.63 (d, 1H), 9.09 (d, 1H), 9.45 (s,1H) 35 N-hydroxy-4-{5-[4-(5- 0.84 (t, 3H), 1.28 (brm, 6H), 1.56 (brm,DMSO-d₆ butyl-2-cyclohexyl-1,3- 6H), 1.77 (brm, 6H), 2.00 (m, 2H),thiazol-4- 2.83 (t, 2H), 2.90 (m, 1H), 4.01 (m, 4H),yl)phenoxy]pentyloxy}- 5.72 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H),benzamidine 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) 36N-hydroxy-4-{5-[4-(5- 0.85 (m, 6H), 1.31 (m, 6H), 1.58 (m, 4H), DMSO-d₆butyl-2-pentyl-1,3- 1.69 (m, 2H), 1.78 (brm, 4H), 2.83 (t, thiazol-4-2H), 2.88 (t, 2H), 4.01 (m, 4H), yl)phenoxy]pentyloxy}- 5.72 (brs, 2H),6.91 (d, 2H), 6.98 (d, benzamidine 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44(s, 1H) 37 N-hydroxy-4-{5-[4-(5- 0.84 (t, 3H), 1.31 (m, 2H), 1.36 (s,9H), DMSO-d₆ butyl-2-t-butyl-1,3- 1.57 (brm, 4H), 1.79 (brm, 4H), 2.83(m, thiazol-4- 2H), 4.01 (m, 4H), 5.74 (brs, 2H), yl)phenoxy]pentyloxy}-6.91 (d, 2H), 6.97 (d, 2H), 7.48 (d, 2H), benzamidine 7.58 (d, 2H), 9.45(s, 1H) 38 N-hydroxy-4-{5-[4-(5- 1.56 (m, 2H), 1.78 (brm, 4H), 2.58 (s,DMSO-d₆ benzyl-2-methyl-1,3- 3H), 4.00 (m, 4H), 4.20 (s, 2H), thiazol-4-5.77 (brs, 2H), 6.91 (d, 2H), 6.98 (d, yl)phenoxy]pentyloxy}- 2H), 7.17(d, 2H), 7.22 (m, 1H), 7.30 (m, benzamidine 2H), 7.52 (d, 2H), 7.57 (d,2H), 9.47 (s, 1H) 39 N-hydroxy-4-{5-[4-(5- 1.28 (d, 6H), 1.57 (m, 2H),1.77 (brm, DMSO-d₆ benzyl-2-isopropyl-1,3- 4H), 3.19 (m, 1H), 4.00 (m,2H), 4.21 (s, thiazol-4- 2H), 5.70 (s, 2H), 6.90 (d, 2H), 6.98 (d,yl)phenoxy]pentyloxy}- 2H), 7.19 (m, 3H), 7.30 (m, 2H), 7.53 (d,benzamidine 2H), 7.56 (d, 2H), 9.44 (s, 1H) 40 N-hydroxy-4-{5-[4-(5-1.58 (m, 2H), 1.79 (brm, 4H), 4.02 (m, DMSO-d₆ benzyl-2-phenyl-1,3- 4H),4.31 (s, 2H), 5.72 (brs, 2H), thiazol-4- 6.91 (d, 2H), 7.03 (d, 2H),7.24 (m, 3H), yl)phenoxy]pentyloxy}- 7.32 (m, 2H), 7.46 (m, 3H), 7.58(d, 2H), benzamidine 7.64 (d, 2H), 7.89 (m, 2H), 9.44 (s, 2H) 41N-hydroxy-4-{5-[4-(5- 1.58 (m, 2H), 1.79 (brm, 4H), 4.02 (m, DMSO-d₆benzyl-2-pyridin-3-yl- 4H), 4.34 (s, 2H), 5.73 (brs, 2H), 1,3-thiazol-4-6.91 (d, 2H), 7.04 (d, 2H), 7.25 (m, 3H), yl)phenoxy]pentyloxy}- 7.33(,. 2H), 7.49 (m, 1H), 7.58 (d, 2H), benzamidine 7.66 (d, 2H), 8.25 (d,1H), 8.63 (d, 1H), 9.08 (s, 1H), 9.45 (s, 1H) 42 N-hydroxy-4-{5-[4-(5-1.65 (m, 2H), 1.86 (m, 4H), 2.72 (s, 3H), DMSO-d₆ (2-chloro-ethyl)-2-3.30 (t, 2H), 3.67 (t, 2H), 4.02 (m, 4H), methyl-1,3-thiazol-4- 5.70 (s,2H), 6.92 (m, 4H), 7.45 (d, 2H), yl)phenoxy]pentyloxy}- 9.43 (s, 1H)benzamidine 43 N-hydroxy-4-{5-[4-(5- 1.58 (brs, 6H), 1.77 (brs, 6H),CDCl₃ cyclopentyl-2-methyl- 2.07 (brs, 2H), 2.62 (s, 3H), 3.30 (m,1,3-thiazol-4- 1H), 3.98 (m, 4H), 6.75~6.92 (m, 4H),yl)phenoxy]pentyloxy}- 7.39~7.60 (m, 4H) benzamidine 44N-hydroxy-4-{5-[4-(5- 0.86 (d, 6H), 1.60 (m 2H), 1.78 (m, 5H), DMSO-d₆isobutyl-2-methyl-1,3- 2.61 (s, 3H), 2.72 (d, 2H), 4.01 (m, 4H),thiazole-4- 5.77 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H),yl)phenoxy]pentyloxy}- 7.45 (d, 2H), 7.59 (d, 2H), 9.47 (s, 1H)benzamidine 45 N-hydroxy-4-{5-[4-(5- 1.14 (m, 2H), 1.48 (brm 6H), 1.69(m, DMSO-d₆ cyclopentylmethyl-2- 2H), 1.78 (brm, 4H), 2.02 (m, 1H),methyl-1,3-thiazol-4- 2.59 (s, 3H), 2.82 (d, 2H), 4.00 (m, 4H),yl)phenoxy]pentyloxy}- 5.70 (s, 2H), 6.90 (d, 2H), 6.97 (d, 2H),benzamidine 7.46 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) 46N-hydroxy-4-{5-[4-(5- 1.11 (m, 2H), 1.27 (t, 3H), 1.52 (brm, DMSO-d₆cyclopentylmethyl-2- 6H), 1.70 (m, 2H), 1.78 (brm, 4H),ethyl-1,3-thiazol-4- 2.03 (m, 1H), 2.83 (d, 2H), 2.92 (q, 2H),yl)phenoxy]pentyloxy}- 4.00 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H),benzamidine 6.98 (d, 2H), 7.46 (d, 2H), 7.79 (d, 2H), 9.44 (s, 1H) 47N-hydroxy-4-{5-[4-(5- 1.11 (m, 2H), 1.31 (d, 6H), 1.49 (brm, DMSO-d₆cyclopentylmethyl-2- 6H), 1.78 (brm, 6H), 2.04 (m, 1H),isopropyl-1,3-thiazol- 2.83 (d, 2H), 3.21 (m, 1H), 4.01 (m, 4H), 4- 5.72(brs, 2H), 6.91 (d, 2H), 6.98 (d, yl)phenoxy]pentyloxy}- 2H), 7.47 (d,2H), 7.57 (d, 2H), 9.44 (s, benzamidine 1H) 48 N-hydroxy-4-{5-[4-(5-1.15 (m, 2H), 1.50 (brm, 6H), 1.78 (brm, DMSO-d₆ cyclopentylmethyl-2-6H), 2.11 (m, 1H), 2.92 (d, 2H), 4.01 (m, phenyl-1,3-thiazol-4- 4H),5.71 (s, 2H), 6.91 (d, 2H), 7.02 (d, yl)phenoxy]pentyloxy}- 2H), 7.46(m, 3H), 7.58 (m, 4H), benzamidine 7.91 (dd, 2H), 9.44 (s, 1H) 49N-hydroxy-4-{5-[4-(5- 1.16 (m, 2H), 1.55 (brm, 6H), 1.78 (brm, DMSO-d₆cyclopentylmethyl-2- 6H), 2.12 (m, 1H), 2.96 (d, 2H), 4.02 (m,pyridin-3-yl-1,3- 4H), 5.71 (brs, 2H), 6.91 (d, 2H), thiazol-4- 7.04 (d,2H), 7.52 (m, 1H), 7.58 (m, 4H), yl)phenoxy]pentyloxy}- 8.26 (m, 1H),8.64 (dd, 1H), 9.10 (d, benzamidine 1H), 9.44 (s, 1H) 50N-hydroxy-4-{5-[4-(5- 1.10 (m, 2H), 1.23 (m, 1H), 1.46 (brm, DMSO-d₆cyclopentylmethyl-2- 11H), 1.77 (brm, 8H), 2.02 (m, 3H),cyclohexyl-1,3-thiazol- 2.83 (d, 2H), 2.90 (m, 1H), 4.00 (m, 4H), 4-5.71 (s, 2H), 6.91 (d, 2H), 6.97 (d, 2H), yl)phenoxy]pentyloxy}- 7.46(d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) benzamidine 51 N-hydroxy-4-{5-[4-(5-0.85 (t, 3H), 1.10 (m, 2H), 1.31 (brm, DMSO-d₆ cyclopentylmethyl-2- 4H),1.52 (brm, 6H), 1.58 (brm, 4H), pentyl-1,3-thiazol-4- 1.70 (brm, 4H),2.03 (m, 1H), 2.83 (d, yl)phenoxy]pentyloxy}- 2H), 2.89 (m, 2H), 4.01(m, 4H), 5.71 (s, benzamidine 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.46 (d,2H), 7.57 (d, 2H), 9.44 (s, 1H) 52 4-{5-[4-(2-methyl-1,3- 1.57 (brm,2H), 1.79 (brm, 4H), 2.68 (s, DMSO-d₆ thiazol-4- 3H), 4.01 (t, 2H), 4.11(t, 2H), 6.96 (d, yl)phenoxy]pentyloxy}- 2H), 7.13 (d, 2H), 7.81 (m, 4H)benzamidine 53 4-{5-[4-(2-isopropyl- 1.35 (d, 6H), 1.56 (brm, 2H), 1.78(brm, DMSO-d₆ 1,3-thiazol-4- 4H), 3.30 (m, 1H), 4.02 (m, 4H), 6.95 (m,yl)phenoxy]pentyloxy}- 4H) 7.77 (s, 1H), 7.83 (m, 4H) benzamidine 544-{5-[4-(2,5-dimethyl- 1.57 (brm, 2H), 1.79 (brm, 4H), 2.68 (s, DMSO-d₆1,3-thiazol-4- 3H), 4.01 (t, 2H), 4.11 (t, 2H), 6.96 (d,yl)phenoxy]pentyloxy}- 2H), 7.12 (d, 2H), 7.73 (s, 1H), 7.81 (m,benzamidine 4H) 55 4-{5-[4-(5-ethyl-2- 1.32 (d, 6H), 1.59 (m, 2H), 1.79(m, 4H), DMSO-d₆ isopropyl-1,3-thiazol- 2.47 (s, 3H), 3.21 (m, 1H), 4.02(t, 2H), 4- 4.09 (t, 2H), 6.98 (d, 2H), 7.09 (d, 2H),yl)phenoxy]pentyloxy}- 7.55 (d, 2H), 7.74 (d, 2H) benzamidine 564-{5-[4-(5-ethyl-2- 1.29 (t, 3H), 1.59 (m, 2H), 1.81 (brm, DMSO-d₆phenyl-1,3-thiazol-4- 4H), 2.95 (q, 2H), 4.04 (t, 2H), 4.11 (t,yl)phenoxy]pentyloxy}- 2H0, 7.03 (d, 2H), 7.15 (d, 2H), 7.47 (m,benzamidine 3H), 7.59 (d, 2H), 7.84 (d, 2H), 7.91 (m, 2H) 57N-hydroxy-4-{5-[4-(2- 1.56 (m, 2H), 1.77 (m, 4H), 3.98 (m, 4H), DMSO-d₆amino-1,3-thiazol-4- 5.72 (s, 2H), 6.80-6.99 (m, 7H), 7.58 (d,yl)phenoxy]pentyloxy}- 2H), 7.69 (d, 2H), 9.46 (s, 1H) benzamidine 58N-hydroxy-4-{5-[4-(2- 1.57 (m, 2H), 1.77 (m, 4H), 2.27 (s, 3H), DMSO-d₆amino-5-methyl-1,3- 3.99 (m, 4H), 5.72 (s, 2H), 6.70 (s, 2H), thiazol-4-6.91 (m, 4H), 7.45 (d, 2H), 7.57 (d, 2H), yl)phenoxy]pentyloxy}- 9.44(s, 1H) benzamidine 59 N-hydroxy-4-{5-[4-(2- 1.56 (m, 2H), 1.78 (m, 2H),2.30 (s, 3H), DMSO-d₆ guanidino-5-methyl-1,3- 4.00 (t, 4H), 5.71 (s,2H), 6.91 (d, 2H), thiazol-4- 6.94 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H),yl)phenoxy]pentyloxy}- 9.44 (s, 1H) benzamidine 60 N-hydroxy-4-{5-[4-(2-1.15 (t, 3H), 1.57 (m, 2H), 1.76 (m, 4H), DMSO-d₆ amino-5-ethyl-1,3-2.68 (q, 2H), 3.99 (m, 4H), 5.69 (s, 2H), thiazol-4- 6.72 (s, 2H), 6.91(m, 4H), 7.39 (d, 2H), yl)phenoxy]pentyloxy}- 7.57 (d, 2H), 9.43 (s, 1H)benzamidine 61 N-hydroxy-4-{5-[4-(2- 1.17 (d, 6H), 1.56 (m, 2H), 1.78(m, 3H), DMSO-d₆ amino-5-isopropyl-1,3- 3.20 (m, 1H), 4.00 (m, 4H), 5.70(brm, thiazol-4- 1H), 6.91 (m, 4H), 7.35 (m, 2H), 7.57 (m,yl)phenoxy]pentyloxy}- 2H), 9.43 (s, 1H) benzamidine 62N-hydroxy-4-{5-[4-(2- 1.17 (d, 6H), 1.56 (brm, 2H), 1.77 (brm, DMSO-d₆guanidino-5-isopropyl- 4H), 3.22 (m, 1H), 4.00 (m, 4H), 5.71 (s,1,3-thiazol-4- 2H), 6.93 (m, 5H), 7.38 (d, 2H), 7.57 (d,yl)phenoxy]pentyloxy}- 2H), 9.44 (s, 1H) benzamidine 63N-hydroxy-4-{5-[4-(2- 0.83 (t, 3H), 1.30 (m, 2H), 1.48 (m, 2H), DMSO-d₆amino-5-butyl-1,3- 1.56 (m, 2H), 1.77 (brm, 4H), 2.65 (t, thiazol-4-2H), 3.99 (m, 4H), 5.73 (brs, 2H), yl)phenoxy]pentyloxy}- 6.72 (s, 2H),6.91 (m, 4H), 7.38 (d, 2H), benzamidine 7.57 (d, 2H), 9.45 (s, 1H) 64N-hydroxy-4-{5-[4-(5- 0.83 (t, 3H), 1.28 (m, 2H), 1.53 (m, 4H), DMSO-d₆butyl-2-guanidino-1,3- 1.78 (m, 4H), 2.69 (m, 2H), 4.00 (m, 4H),thiazol-4- 5.73 (brs, 2H), 6.91 (d, 2H), 6.95 (d, yl)phenoxy]pentyloxy}-2H), 7.42 (d, 2H), 7.57 (d, 2H), 9.45 (s, benzamidine 1H) 65N-hydroxy-4-{5-[4-(2- 1.55 (brm,, 2H), 1.77 (brm, 4H), 3.98 (m, DMSO-d₆amino-5-benzyl-1,3- 4H), 4.02 (s, 1H), 5.79 (s, 2H), 6.79 (s, thiazol-4-2H), 6.91 (m, 4H), 7.19 (m, 3H), 7.29 (m, yl)phenoxy]pentyloxy}- 2H),7.43 (d, 2H), 7.57 (d, 2H), 9.47 (s, benzamidine 1H) 66N-hydroxy-4-{5-[4-(5- 1.55 (m, 2H), 1.77 (brm, 4H), 4.99 (m, DMSO-d₆benzyl-2-guanidino-1,3- 4H), 4.05 (s, 2H), 5.71 (s, 2H), 4.92 (m,thiazol-4- 4H), 7.19 (m, 3H), 7.29 (m, 2H), 7.45 (d,yl)phenoxy]pentyloxy}- 2H), 7.57 (d, 2H), 9.44 (s, 1H) benzamidine 67N-hydroxy-4-{5-[4-(2- 1.09 (brm, 2H), 1.48 (brm, 4H), 1.56 (m, DMSO-d₆amino-5- 2H), 1.69 (m, 2H), 1.77 (brm, 4H), cyclopentylmethyl-1,3- 1.97(m, 1H), 2.65 (d, 2H), 3.98 (m, 4H), thiazol-4- 5.70 (s, 2H), 6.72 (s,2H), 6.90 (m, 4H), yl)phenoxy]pentyloxy}- 7.38 (d, 2H), 7.57 (d, 2H),9.44 (s, 1H) benzamidine 68 N-hydroxy-4-{5-[4-(5- 0.84 (t, 3H), 1.11 (m,2H), DMSO-D₆ cyclopentylmethyl-2-(1- 1.43-1.78 (brm, 17H), 2.04 (m, 4H),2.24 (m, propyl-piperidin-4-yl)- 2H), 2.85 (m, 5H), 4.01 (m, 4H), 5.70(s, 1,3-thiazol-4- 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.47 (d,yl)phenoxy]pentyloxy}- 2H), 7.57 (d, 2H), 9.44 (s, 1H) benzamidine 69N-hydroxy-4-{5-[4-(2- 1.11 (d, 6H), 1.59 (m, 2H), 1.79 (m, 4H), DMSO-d₆(isobutyryl)amino-5- 2.42 (s, 3H), 2.72 (m, 1H), 4.02 (m, 4H),methyl-1,3-thiazol-4- 5.72 (s, 2H), 6.93 (d, 2H), 7.00 (d, 2H),yl)phenoxy]pentyloxy}- 7.56 (m, 4H), 9.45 (s, 1H), 12.00 (s, 1H)benzamidine 70 N-hydroxy-4-{5-[4-(5- 1.25 (d, 6H), 1.58 (m, 2H), 1.80(m, 4H), DMSO-d₆ isopropyl-2- 2.50 (m, 4H), 3.33 (m, 1H), 3.60 (m, 4H),morpholinomethyl-1,3- 3.76 (s, 2H), 4.01 (m, 4H), 5.70 (s, 2H),thiazol-4- 7.00 (m, 4H), 7.45 (d, 2H), 7.60 (d, 2H),yl)phenoxy]pentyloxy}- 9.44 (s, 1H) benzamidine 71 N-hydroxy-4-{5-[4-(2-1.56 (m, 2H), 1.78 (brm, 4H), 3.92 (s, DMSO-d₆ aminomethyl-5-benzyl-2H), 4.00 (m, 4H), 4.21 (s, 2H), 5.70 (s, 1,3-thiazol-4- 2H), 6.90 (d,2H), 6.97 (d, 2H), 7.21 (m, yl)phenoxy]pentyloxy}- 3H), 7.30 (m, 2H),7.52 (d, 2H), 7.57 (d, benzamidine 2H), 9.44 (s, 1H) 72N-hydroxy-4-{5-[4-(5- 0.84 (t, 3H), 1.42 (m, 2H), 1.56 (m, 2H), DMSO-d₆methyl-2-(1-propyl- 1.67 (m, 2H), 1.78 (brm, 4H), 2.00 (m,piperidin-4-yl)-1,3- 4H), 2.24 (m, 2H), 2.46 (s, 3H), 2.89 (m,thiazol-4- 3H), 4.00 (m, 4H), 5.71 (m, 2H), 6.90 (d,yl)phenoxy]pentyloxy}- 2H), 6.98 (d, 2H), 7.56 (m, 4H), 9.44 (s,benzamidine 1H) 73 N-hydroxy-4-{5-[4-(5- 1.25 (d, 6H), 1.57 (m, 2H),1.79 (m, 4H), DMSO-d₆ isopropyl-2- 3.35 (m, 1H), 3.96-4.04 (m, 6H), 5.74(s, aminomethyl-1,3- 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.43 (d,thiazol-4- 2H), 7.58 (d, 2H) yl)phenoxy]pentyloxy}- benzamidine 74N-hydroxy-4-{5-[4-(5- 1.61 (m, 2H), 1.81 (m, 4H), 2.66 (s, 3H), CDCl₃vinyl-2-methyl-1,3- 3.95 (m, 4H), 5.16 (S, 1H), 5.17 (d, 1H), thiazol-4-5.42 (d, 1H), 6.84 (m, 3H), 6.92 (d, 2H), yl)phenoxy]pentyloxy}- 7.51(d-d, 4H) benzamidine 75 N-hydroxy-4-{5-[4-(5- 1.58 (m, 2H), 1.79 (m,4H), 2.63 (s, 3H), DMSO-d₆ hydroxymethyl-2-methyl- 4.01 (m, 4H), 4.12(t, 1H), 4.67 (m, 2H), 1,3-thiazol-4- 5.70 (brs, 2H), 6.98 (m, 2H), 7.50(m, 2H), yl)phenoxy]pentyloxy}- 7.58 (m, 2H), 8.23 (s, 1H) benzamidine76 N-hydroxy-4-{5-[4-(5- 1.57 (m, 2H), 1.80 (m, 4H), 2.65 (s, 3H),DMSO-d₆ methoxymethyl-2-methyl- 3.32 (s, 3H), 4.01 (m, 4H), 4.58 (s,2H), 1,3-thiazol-4- 6.93 (m, 2H), 7.01 (m, 2H), 7.56 (m, 4H),yl)phenoxy]pentyloxy}- 9.45 (brs, 1H) benzamidine 77N-hydroxy-4-{5-[4-(5- 1.57 (m, 2H), 1.79 (m, 4H), 3.36 (m, 2H), DMSO-d₆(2-chloroethyl)-2- 3.77 (m, 2H), 4.00 (m, 4H), 5.73 (s, 2H),amino-1,3-thiazol-4- 6.91 (m, 4H), 7.42 (d, 2H), 7.58 (d, 2H),yl)phenoxy]pentyloxy}- 9.47 (s, 1H) benzamidine 78 N-hydroxy-4-{5-[4-(5-1.58 (m, 2H), 1.79 (m, 4H), 4.01 (m, 4H), DMSO-d₆ vinyl-2-amino-1,3-6.82-7.75 (m, 11H) thiazol-4- yl)phenoxy]pentyloxy}- benzamidine 79N-hydroxy-4-{5-[4-(5- 1.59 (m, 2H), 1.81 (m, 4H), 4.05 (m, 4H), DMSO-d₆vinyl-2-(pyridin-3-yl)- 5.44 (d, 1H), 5.71 (d, 1H), 5.85 (brs,1,3-thiazol-4- 2H), 6.94 (m, 3H), 7.07 (m, 2H), 7.61 (m,yl)phenoxy]pentyloxy}- 4H), 8.33 (m, 1H), 8.68 (m, 1H), benzamidine 9.16(brs, 1H), 9.52 (brs, 1H) 80 N-hydroxy-4-{5-[4-(5- 1.60 (m, 2H), 1.81(m, 4H), 3.44 (m, 2H), DMSO-d₆ (2-chloroethyl)-2- 3.94 (m, 2H),4.02-4.06 (m, 4H), (pyridin-3-yl)-1,3- 5.75 (brs, 2H), 6.91 (m, 2H),7.06 (m, thiazol-4- 2H), 7.61 (m, 4H), 8.30 (m, 1H), 8.68 (m,yl)phenoxy]pentyloxy}- 1H), 9.13 (m, 1H), 9.46 (m, 1H) benzamidine 81N-hydroxy-4-{5-[4-(2- 1.40 (m, 2H), 1.55-1.59 (m, 4H), DMSO-d₆amino-5-cyclopentyl- 1.77-1.81 (m, 6H), 2.01 (m, 2H), 3.22-3.31 (m,1,3-thiazol-4- 1H), 4.00-4.02 (m, 4H), 5.72 (s, 2H),yl)phenoxy]pentyloxy}- 6.92 (m, 4H), 7.57 (d, 2H), 7.83 (d, 2H)benzamidine 82 N-hydroxy-4-{5-[4-(5- 1.21 (t, 3H), 1.58 (m, 2H), 1.78(m, 4H), ethyl-2-aminomethyl- 2.85 (q, 2H), 3.93 (s, 2H), 4.00 (m, 4H),1,3-thiazol-4- 5.70 (s, 2H), 6.90 (d, 2H), 6.97 (d, 2H),yl)phenoxy]pentyloxy}- 7.48 (d, 2H), 7.58 (d, 2H), 9.43 (s, 1H)benzamidine 83 N-hydroxy-4-{5-[4-(5- 1.25 (d, 6H), 1.57 (m, 2H), 1.80(m, 4H), DMSO-d₆ isopropyl-2-(piperidin- 1.91 (m, 2H), 2.17 (m, 2H),3.05 (m, 2H), 3-yl)-1,3-thiazol-4- 3.37 (m, 4H), 4.02-4.09 (m, 4H), 7.00(d, yl)phenoxy]pentyloxy}- 2H), 7.13 (d, 2H), 7.44 (d, 2H), 7.67 (d,benzamidine 2H) 84 N-hydroxy-4-{5-[4-(2- 1.17 (t, 3H), 1.55 (brm, 2H),1.77 (brm, DMSO-d₆ ethylamino-1,3-thiazol- 2H), 3.25 (m, 2H), 3.99 (m,4H), 5.73 (s, 4- 2H), 6.84 (s, 1H), 6.90 (m, 4H), 7.57 (d,yl)phenoxy]pentyloxy}- 2H), 7.71 (d, 2H) benzamidine 85N-hydroxy-4-{5-[4-(2- 1.20 (t, 3H), 1.55 (brm, 2H), 1.77 (brm, DMSO-d₆ethanesulphonylamino- 4H), 3.02 (q, 2H), 4.00 (m, 4H), 1,3-thiazol-4-5.77 (brm, 2H), 6.91 (d, 2H), 6.98 (d, yl)phenoxy]pentyloxy}- 2H), 7.00(s, 1H), 7.57 (d, 2H), 7.65 (d, benzamidine 2H), 9.47 (brs, 1H), 12.86(s, 1H) 86 N-hydroxy-4-{5-[4-(5- 1.56 (m, 2H), 1.77 (m, 4H), 2.29 (s,3H), DMSO-d₆ methyl-2-methylamino- 2.77 (d, 3H), 3.99 (m, 4H), 5.72 (s,2H), 1,3-thiazol-4- 6.91 (m, 4H), 7.22 (m, 1H), 7.48 (d, 2H),yl)phenoxy]pentyloxy}- 7.50 (d, 2H), 9.44 (s, 1H) benzamidine 87N-hydroxy-4-{5-[4-(2- 1.12 (t, 3H), 1.56 (m, 2H), 1.78 (m, 4H), DMSO-d₆ethylamino-5-methyl- 2.28 (s, 3H), 3.18 (p, 2H), 3.99 (t, 4H),1,3-thiazol-4- 5.72 (s, 2H), 6.94 (m, 4H), 7.27 (t, 1H),yl)phenoxy]pentyloxy}- 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H)benzamidine 88 N-hydroxy-4-{5-[4-(5- 0.89 (t, 3H), 1.54 (m, 4H), 1.78(m, 4H), methyl-2-propylamino- 2.28 (s, 3H), 3.12 (m, 2H), 3.99 (m, 4H),1,3-thiazol-4- 5.72 (s, 1H), 6.92 (m, 4H), 7.32 (t, 1H)yl)phenoxy]pentyloxy}- 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H)benzamidine 89 N-hydroxy-4-{5-[4-(5- 1.15 (m, 2H), 1.57 (brm, 6H), 1.77(brm, DMSO-d₆ cyclopentylmethyl-2-(3- 6H), 2.10 (m, 1H), 2.85 (d, 2H),4.00 (m, pyridylcarbonyl)amino- 4H), 5.72 (brs, 2H), 6.91 (d, 2H),1,3-thiazol-4- 7.00 (d, 2H), 7.51 (d, 2H), 7.58 (d, 2H),yl)phenoxy]pentyloxy}- 7.38 (m, 1H), 8.40 (d, 1H), 8.77 (d, 1H),benzamidine 9.19 (s, 1H), 9.44 (s, 1H), 12.83 (s, 1H) 90N-hydroxy-4-{5-[4-(2- 1.56 (brm, 2H), 1.78 (brm, 4H), 2.42 (s, DMSO-d₆hydroxyacetylamino-5- 3H), 4.01 (m, 4H), 4.10 (d, 2H), 5.47 (t,methyl-1,3-thiazol-4- 1H), 5.73 (brs, 2H), 6.92 (d, 2H),yl)phenoxy]pentyloxy}- 6.98 (d, 2H), 7.55 (m, 4H), 9.45 (s, 1H),benzamidine 11.67 (s, 1H) 91 N-hydroxy-4-{5-[4-(5- 1.57 (brm, 4H), 1.79(brm, 4H), 2.48 (s, DMSO-d₆ methyl-2-(4- 3H), 4.02 (m, 4H), 5.73 (brm,2H), pyridylcarbonyl)amino- 6.91 (d, 2H), 7.01 (d, 2H), 7.58 (m, 4H),1,3-thiazol-4- 7.98 (dd, 2H), 8.78 (dd, 2H), 9.45 (s,yl)phenoxy]pentyloxy}- 1H) benzamidine 92 N-hydroxy-4-{5-[4-(5- 1.58 (m,2H), 1.79 (m, 4H), 2.46 (s, 3H), DMSO-d₆ methyl-2-(3- 4.01 (m, 4H), 5.74(s, 2H), 6.91 (d, 2H), pyridylcarbonyl)amino- 7.00 (d, 2H), 7.57 (m,4H), 8.41 (d, 1H), 1,3-thiazol-4- 8.77 (d, 1H), 9.20 (d, 1H), 9.46 (brs,yl)phenoxy]pentyloxy}- 1H), 12.80 (brs, 1H) benzamidine 93N-hydroxy-4-{5-[4-(2- 0.94 (t, 3H), 1.56 (m, 2H), 1.78 (brm, DMSO-d₆ethanesulphonylamino-5- 4H), 2.18 (s, 3H), 2.98 (q, 2H), 4.01 (m,methyl-1,3-thiazol-4- 4H), 5.73 (s, 2H), 6.90 (d, 2H), 7.01 (d,yl)phenoxy]pentyloxy}- 2H), 7.38 (d, 2H), 7.57 (d, 2H), 9.44 (s,benzamidine 1H), 12.52 (s, 1H) 94 N-hydroxy-4-{5-[4-(2- 1.58 (m, 2H),1.80 (m, 4H), 2.30 (s, 3H), DMSO-d₆ (2-methoxyethyl)amino- 3.26 (s, 3H),3.39 (m, 2H), 3.37 (m, 2H), 5-methyl-1,3-thiazol-4- 4.01 (m, 4H), 5.71(s, 2H), 6.90 (d, 2H), yl)phenoxy]pentyloxy}- 6.96 (d, 2H), 7.48 (d,2H), 7.58 (d, 2H), benzamidine 9.44 (s, 1H) 95 N-hydroxy-4-{5-[4-(2-1.13 (t, 3H), 1.21 (t, 3H), 1.57 (m, 2H), DMSO-d₆ethanesulphonylamino-5- 1.78 (brm, 4H), 2.59 (q, 2H), 2.99 (q,ethyl-1,3-thiazol-4- 2H), 4.01 (m, 4H), 5.70 (s, 2H), 6.90 (s,yl)phenoxy]pentyloxy}- 2H), 7.01 (d, 2H), 7.35 (d, 2H), 7.57 (d,benzamidine 2H), 9.43 (s, 1H), 12.50 (brs, 1H) 96 N-hydroxy-4-{5-[4-(5-1.15 (t, 3H), 1.57 (m, 2H), 1.78 (m, 4H), DMSO-d₆ ethyl-2-methylamino-2.70 (q, 2H), 2.78 (d, 3H), 3.99 (m, 4H), 1,3-thiazol-4- 5.80 (brs, 2H),6.92 (m, 4H), 7.25 (q, yl)phenoxy]pentyloxy}- 1H), 7.42 (d, 2H), 7.58(d, 2H), 9.48 (s, benzamidine 1H) 97 N-hydroxy-4-{5-[4-(5- 1.41 (m, 6H),1.57 (m, 2H), 1.78 (t, 4H), DMSO-d₆ ethyl-2-ethylamino-1,3- 2.69 (q,2H), 3.19 (q, 2H), 3.99 (t, 4H), thiazol-4- 5.69 (s, 2H), 6.92 (m, 4H),7.30 (t, 1H), yl)phenoxy]pentyloxy}- 7.41 (d, 2H), 7.57 (d, 2H), 9.43(s, 1H) benzamidine 98 N-hydroxy-4-{5-[4-(5- 0.89 (t, 3H), 1.15 (t, 3H),1.55 (brm, DMSO-d₆ ethyl-2-propylamino- 4H), 1.77 (brm, 4H), 2.68 (q,2H), 1,3-thiazol-4- 3.12 (m, 2H), 3.98 (m, 4H), 5.72 (s, 2H),yl)phenoxy]pentyloxy}- 6.92 (m, 4H), 7.35 (t, 1H), 7.40 (d, 2H),benzamidine 7.57 (d, 2H), 9.44 (s, 1H) 99 N-hydroxy-4-{5-[4-(5- 1.23 (t,3H), 1.57 (m, 2H), 1.78 (brm, DMSO-d₆ ethyl-2- 4H), 2.84 (q, 2H), 3.33(s, 3H), 4.00 (m, methoxyacetylamino-1,3- 4H), 4.11 (s, 2H), 5.70 (s,2H), 6.90 (d, thiazol-4- 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.82 (d,yl)phenoxy]pentyloxy}- 2H), 9.43 (s, 1H), 11.96 (s, 1H) benzamidine 100N-hydroxy-4-{5-[4-(5- 1.26 (t, 3H), 1.57 (m, 2H), 1.79 (brm, DMSO-d₆ethyl-2-(4- 4H), 2.88 (q, 2H), 4.00 (m, 4H), 5.74 (s,pyridylcarbonyl)amino- 2H), 6.91 (d, 2H), 7.01 (d, 2H), 7.52 (d,1,3-thiazol-4- 2H), 7.55 (d, 2H), 7.98 (d, 2H), 8.79 (d,yl)phenoxy]pentyloxy}- 2H), 9.45 (s, 1H), 12.92 (s, 1H) benzamidine 101N-hydroxy-4-{5-[4-(5- 1.26 (t, 3H), 1.57 (brm, 2H), 1.79 (brm, DMSO-d₆ethyl-2-(3- 4H), 2.88 (q, 2H), 4.00 (m, 4H), pyridylcarbonyl)amino- 5.71(brs, 2H), 6.91 (d, 2H), 7.01 (d, 1,3-thiazol-4- 2H), 7.56 (m, 5H), 8.40(m, 1H), yl)phenoxy]pentyloxy}- 8.77 (dd, 1H), 9.20 (d, 1H), 9.43 (s,benzamidine 1H), 12.82 (s, 1H) 102 N-hydroxy-4-{5-[4-(5- 1.14 (t, 3H),1.60 (m, 2H), 1.78 (m, 4H), DMSO-d₆ ethyl-2-(2- 2.69 (m, 2H), 3.26 (s,3H), 3.40 (m, 2H), methoxyethyl)amino-1,3- 3.38 (m, 2H), 4.02 (m, 4H),5.67 (s, 2H), thiazol-4- 5.75 (s, 1H), 6.90~7.00 (m, 4H), 7.40 (d,yl)phenoxy]pentyloxy}- 2H), 7.58 (d, 2H), 9.45 (s, 1H) benzamidine 103N-hydroxy-4-{5-[4-(5- 1.17 (d, 6H), 1.56 (brm, 2H), 1.77 (brm, DMSO-d₆isopropyl-2- 2H), 2.77 (d, 3H), 3.21 (m, 1H), 5.72 (s, methylamino-1,3-2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.25 (m, thiazol-4- 1H), 7.38 (d, 2H),7.57 (d, 2H), 9.44 (s, yl)phenoxy]pentyloxy}- 1H) benzamidine 104N-hydroxy-4-{5-[4-(2- 0.85 (m, 3H), 1.17 (d, 6H), 1.58 (m, 2H), DMSO-d₆ethylamino-5-isopropyl- 1.82 (m, 4H), 3.20 (m, 3H), 4.04 (m, 4H),1,3-thiazol-4- 6.95 (m, 4H), 7.39 (m, 2H), 7.82 (m, 2H)yl)phenoxy]pentyloxy}- benzamidine 105 N-hydroxy-4-{5-[4-(5- 0.83 (t,3H), 1.30 (m, 2H), 1.48 (m, 2H), DMSO-d₆ butyl-2-methylamino- 1.56 (m,2H), 1.77 (m, 4H), 2.67 (t, 2H), 1,3-thiazol-4- 2.78 (d, 3H), 4.01 (m,4H), 5.72 (brs, yl)phenoxy]pentyloxy}- 2H), 6.92 (m, 4H), 7.26 (m, 1H),7.41 (d, benzamidine 2H), 7.58 (d, 2H), 9.44 (s, 1H) 106N-hydroxy-4-{5-[4-(5- 0.83 (t, 3H), 1.13 (t, 3H), 1.28 (m, 2H), DMSO-d₆butyl-2-ethylamino-1,3- 1.53 (m, 4H), 1.78 (m, 4H), 2.64 (t, 2H),thiazol-4- 3.18 (m, 2H), 3.99 (m, 4H), 5.75 (brs, yl)phenoxy]pentyloxy}-2H), 6.92 (m, 4H), 7.31 (t, 1H), 7.40 (d, benzamidine 2H), 7.57 (d, 2H),9.46 (s, 1H) 107 N-hydroxy-4-{5-[4-(5- 1.55 (m, 2H), 1.76 (brm, 4H),2.77 (d, DMSO-d₆ benzyl-2-methylamino- 3H), 3.98 (m, 4H), 4.03 (s, 2H),1,3-thiazol-4- 5.72 (brs, 2H), 6.91 (m, 4H), 7.20 (m,yl)phenoxy]pentyloxy}- 3H), 7.29 (m, 3H), 7.46 (d, 2H), 7.57 (d,benzamidine 2H), 9.44 (s, 1H) 108 N-hydroxy-4-{5-[4-(5- 1.14 (t, 3H),1.55 (m, 2H), 1.77 (brm, DMSO-d₆ benzyl-2-ethylamino- 4H), 3.18 (m, 2H),4.00 (m, 4H), 4.03 (s, 1,3-thiazol-4- 2H), 6.94 (m, 4H), 7.17 (m, 3H),7.29 (m, yl)phenoxy]pentyloxy}- 2H), 7.39 (t, 1H), 7.45 (d, 2H), 7.58(d, benzamidine 2H), 9.64 (s, 1H) 109 N-hydroxy-4-{5-[4-(5- 1.10 (brm,2H), 1.49 (brm, 4H), 1.56 (m, DMSO-d₆ cyclopentylmethyl-2- 2H), 1.69 (m,2H), 1.78 (m, 4H), 1.97 (m, methylamino-1,3- 1H), 2.66 (d, 2H), 2.78 (d,3H), 3.99 (m, thiazol-4- 4H), 5.71 (s, 2H), 6.92 (m, 4H), 7.25 (m,yl)phenoxy]pentyloxy}- 1H), 7.40 (d, 2H), 7.57 (d, 2H), 9.44 (s,benzamidine 1H) 110 N-hydroxy-4-{5-[4-(5- 1.13 (m, 5H), 1.49 (m, 6H),1.69 (m, 2H), DMSO-d₆ cyclopentylmethyl-2- 1.77 (m, 4H), 1.97 (m, 1H),2.66 (d, 2H), ethylamino-1,3-thiazol- 3.19 (m, 2H), 3.99 (m, 4H), 5.70(s, 2H), 4- 6.91 (m, 4H), 7.29 (t, 1H), 7.40 (d, 2H),yl)phenoxy]pentyloxy}- 7.57 (d, 2H), 9.44 (s, 1H) benzamidine 111N-hydroxy-4-{5-[4-(5- 0.88 (t, 3H), 1.10 (brm, 2H), 1.55 (brm, DMSO-d₆cyclopentylmethyl-2- 8H), 1.77 (brm, 6H), 1.97 (m, 1H), propylamino-1,3-2.65 (d, 2H), 3.11 (m, 2H), 3.99 (m, 4H), thiazol-4- 5.70 (s, 2H), 6.90(d, 2H), 6.92 (d, 2H), yl)phenoxy]pentyloxy}- 7.33 (t, 1H), 7.39 (d,2H), 7.57 (d, 2H), benzamidine 9.44 (s, 1H) 112 N-hydroxy-4-{5-[4-(5-1.55 (m, 2H), 1.49 (brm, 6H), 1.77 (brm, DMSO-d₆ cyclopentylmethyl-2-(4-6H), 2.10 (m, 1H), 2.86 (d, 2H), 4.00 (m, pyridylcarbonyl)amino- 4H),5.74 (s, 2H), 6.91 (d, 2H), 7.01 (d, 1,3-thiazol-4- 2H), 7.51 (d, 2H),7.58 (d, 2H), 7.97 (d, yl)phenoxy]pentyloxy}- 2H), 8.79 (d, 2H), 9.46(s, 1H), benzamidine 12.91 (s, 1H) 113 N-hydroxy-4-{5-[4-(5- 0.89 (t,3H), 1.55-1.62 (m, 8H), DMSO-d₆ cyclopentyl-2- 1.77-1.80 (m, 8H),3.31-3.37 (m, 3H), propylamino-1,3- 4.00-4.02 (m, 4H), 6.90-7.05 (m,4H), thiazol-4- 7.39-7.80 (m, 4H) yl)phenoxy]pentyloxy}- benzamidine 114N-hydroxy-4-{5-[4-(5- 0.82 (d, 6H), 1.17-1.25 (m, 2H), DMSO-d₆isopropyl-2-[(pyridin- 1.78-1.80 (m, 4H), 3.25 (m, 1H), 3.37 (s, 2H),3-ylmethyl)amino]-1,3- 4.01 (m, 4H), 6.94-7.83 (m, 12H) thiazol-4-yl)phenoxy]pentyloxy}- benzamidine 115 N-hydroxy-4-{5-[4-(5- 1.58 (m,2H), 1.80 (m, 4H), 2.81 (s, 3H), DMSO-d₆ (2-chloroethyl)-2- 3.13 (m,2H), 3.78 (m, 2H), 4.01 (m, 4H), methylamino-1,3- 5.73 (m, 2H), 6.93 (m,4H), 7.44 (m, 2H), thiazol-4- 7.59 (m, 2H), 9.46 (s, 1H)yl)phenoxy]pentyloxy}- benzamidine 116 N-hydroxy-4-{5-[4-(2- 1.57 (m,2H), 1.77-1.81 (m, 4H), 2.86 (d, DMSO-d₆ methylamino-1,3- 3H), 3.99-4.01(m, 4H), 5.72 (s, 2H), thiazol-4- 6.88-6.93 (m, 5H), 7.59 (d, 2H), 7.74(d, yl)phenoxy]pentyloxy}- 2H), 9.46 (s, 1H) benzamidine 117N-hydroxy-4-{5-[4-(5- 1.24 (t, 3H), 1.57 (m, 2H), 1.79 (m, 4H), DMSO-d₆ethyl-2-(pyridin-3- 2.87 (q, 2H), 3.79 (s, 2H), 3.91 (s, 2H),ylmethyl)amino-1,3- 4.02 (m, 4H), 5.74 (s, 1H), 6.94 (d-d, thiazol-4-4H), 7.35 (m, 1H), 7.48 (d, 2H), 7.77 (d, yl)phenoxy]pentyloxy}- 1H),7.82 (d, 2H), 8.45 (d, 1H), 8.54 (s, benzamidine 1H) 118N-hydroxy-4-{5-[4-(2- 1.20 (t, 3H), 1.57 (m, 2H), 1.79 (m, 4H), DMSO-d₆(ethanesulphonyl- 3.50 (m, 5H), 4.01 (m, 4H), 5.71 (s, 2H),methyl-amino)-1,3- 6.96 (m, 4H), 7.55 (m, 2H), 7.81 (m, 3H), thiazol-4-9.44 (s, 1H) yl)phenoxy]pentyloxy}- benzamidine 119N-hydroxy-4-[5-(4-{2- 1.56 (brm, 2H), 1.78 (brm, 4H), 2.43 (m, DMSO-d₆[methyl-(2- 4H), 2.55 (m, 2H), 3.05 (s, 3H), 3.52 (m,morpholinoethyl)amino]- 4H), 3.60 (m, 2H), 3.99 (brm, 4H),1,3-thiazol-4- 5.70 (s, 2H), 6.91 (m, 4H), 6.95 (s, 1H),yl}phenoxy)pentyloxy]- 7.57 (d, 2H), 7.73 (d, 2H), 9.44 (s, 1H)benzamidine 120 N-hydroxy-4-[5-(4-{2- 1.56 (m, 2H), 1.78 (brm, 4H), 2.31(s, DMSO-d₆ [(2-hydroxyethyl)- 3H), 3.02 (s, 3H), 3.44 (t, 2H), 3.59 (q,methyl-amino]-5-methyl- 2H), 4.00 (t, 4H), 4.79 (t, 1H), 5.71 (s,1,3-thiazol-4- 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.48 (d,yl}phenoxy)pentyloxy]- 2H), 7.57 (d, 2H), 9.43 (s, 1H) benzamidine 121N-hydroxy-4-[5-(4-{2- 1.14 (t, 3H), 1.56 (m, 2H), 1.78 (brm, DMSO-d₆[ethyl-(2- 4H), 2.31 (s, 3H), 3.41 (m, 4H), 3.58 (m,hydroxyethyl)-amino]-5- 2H), 4.00 (m, 4H), 4.82 (t, 1H), 5.73 (s,methyl-1,3-thiazol-4- 2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.48 (d,yl}phenoxy)pentyloxy]- 2H), 7.57 (d, 2H), 9.45 (s, 1H) benzamidine 122N-hydroxy-4-[5-(4-{2- 1.59 (m, 2H), 1.79 (m, 4H), 2.32 (s, 3H), DMSO-d₆[bis-(2-methoxyethyl)- 3.26 (s, 6H), 3.55 (s, 8H), 4.03 (m, 4H),amino]-5-methyl-1,3- 5.70 (s, 2H), 6.91 (d, 2H), 6.95 (d, 2H),thiazol-4- 7.49 (d, 2H), 7.82 (d, 2H), 9.44 (s, 1H)yl}phenoxy)pentyloxy]- benzamidine 123 N-hydroxy-4-[5-(4-{5- 1.56 (m,2H), 1.77 (brm, 4H), 2.32 (s, DMSO-d₆ methyl-2-[methyl-(2- 3H), 2.41(brm, 4H), 2.51 (m, 2H), morpholinoethyl)- 2.99 (s, 3H), 3.51 (brm, 4H),3.99 (t, amino]-1,3-thiazol-4- 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d,yl}phenoxy)pentyloxy]- 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.44 (s,benzamidine 1H) 124 N-hydroxy-4-[5-(4-{2- 1.15 (t, 3H), 1.56 (m, 2H),1.77 (brm, DMSO-d₆ [ethyl-1-(2- 4H), 2.31 (s, 3H), 2.42 (brm, 4H),morpholinoethyl)- 2.52 (m, 2H), 3.40 (m, 2H), 3.49 (m, 2H),amino]-5-methyl-1,3- 3.54 (brm, 4H), 3.99 (m, 4H), 5.71 (brs, thiazol-4-2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.48 (d, yl}phenoxy)pentyloxy]- 2H),7.57 (d, 2H), 9.44 (s, 1H) benzamidine 125 N-hydroxy-4-{5-(4-[2- 1.57(m, 2H), 1.77 (brm, 4H), 2.29 (s, DMSO-d₆ (benzyl-methyl-amino)- 3H),2.98 (s, 3H), 3.99 (m, 4H), 4.64 (s, 5-methyl-1,3-thiazol-4- 2H), 5.70(s, 2H), 6.90 (d, 2H), 6.94 (d, yl]phenoxy)pentyloxy}- 2H), 7.30 (m,5H), 7.51 (d, 2H), 7.57 (d, benzamidine 2H), 9.44 (s, 1H) 126N-hydroxy-4-[5-{4-[5- 1.56 (brm, 2H), 1.77 (brm, 4H), 2.33 (s, DMSO-d₆methyl-2-(methyl- 3H), 3.00 (s, 3H), 4.00 (m, 4H), 4.68 (s,pyridin-3-yl-methyl- 2H), 5.71 (s, 2H), 6.90 (d, 2H), 6.95 (d,amino)-1,3-thiazol-4- 2H), 7.36 (m, 1H), 7.51 (d, 2H), 7.57 (d,yl]phenoxy}pentyloxy]- 2H), 7.72 (d, 1H), 8.48 (d, 1H), 8.55 (s,benzamidine 1H), 9.44 (s, 1H) 127 N-hydroxy-4-[5-{4-[2- 1.12 (t, 3H),1.56 (brm, 2H), 1.77 (brm, DMSO-d₆ (benzyl-ethyl-amino)-5- 4H), 2.31 (s,3H), 3.40 (q, 2H), 3.99 (m, methyl-1,3-thiazol-4- 4H), 4.62 (s, 2H),5.71 (s, 2H), 6.90 (d, yl]phenoxy}pentyloxy]- 2H), 6.94 (d, 2H), 7.26(m, 1H), 7.31 (m, benzamidine 4H) 7.50 (d, 2H), 7.57 (d, 2H), 9.44 (s,1H) 128 N-hydroxy-4-[5-(4-{2- 1.57 (m, 2H), 1.80 (m, 4H), 2.24 (s, 3H),DMSO-d₆ [bis-(2-hydroxyethyl)- 3.0~4.5 (brs, 2H), 3.67 (s, 8H), 4.05 (m,amino]-5-methyl-1,3- 4H), 5.72 (s, 2H), 7.03 (d, 2H), 7.12 (d,thiazol-4- 2H), 7.44 (d, 2H), 7.82 (d, 2H), 9.45 (s,yl}phenoxy)pentyloxy]- 1H) benzamidine 129 N-hydroxy-4-[5-(4-{5- 1.17(t, 3H), 1.57 (m, 2H), 1.78 (brm, DMSO-d₆ ethyl-2-[(2- 4H), 2.72 (q,2H), 3.03 (s, 3H), 3.45 (t, hydroxyethyl)-methyl- 2H), 3.59 (m, 2H),4.01 (m, 4H), 4.79 (t, amino]-1,3-thiazol-4- 1H), 5.70 (s, 2H), 6.90 (d,2H), 6.96 (d, yl}phenoxy)pentyloxy]- 2H), 7.42 (d, 2H), 7.57 (d, 2H),9.43 (s, benzamidine 1H) 130 N-hydroxy-4-[5-(4-{5- 1.15 (m, 6H), 1.56(brm, 2H), 1.76 (brm, DMSO-d₆ ethyl-2-[ethyl-(2- 4H), 2.71 (q, 2H), 3.43(m, 4H), 4.00 (t, hydroxyethyl)-amino]- 4H), 4.81 (t, 1H), 5.70 (s, 2H),6.90 (d, 1,3-thiazol-4- 2H), 6.94 (d, 2H), 7.42 (d, 2H), 7.81 (d,yl}phenoxy)pentyloxy]- 2H), 9.43 (s, 1H) benzamidine 131N-hydroxy-4-[5-(4-{5- 1.17 (t, 3H), 1.56 (m, 2H), 1.77 (m, 4H), DMSO-d₆ethyl-2-[methyl-(2- 2.41 (brm, 4H), 2.51 (m, 2H), 2.72 (q,morpholinoethyl)- 2H), 3.00 (s, 3H), 3.53 (brm, 6H),amino]-1,3-thiazol-4- 3.99 (t, 4H), 5.70 (s, 2H), 6.90 (d, 2H),yl}phenoxy)pentyloxy]- 6.94 (d, 2H), 7.42 (d, 2H), 7.57 (d, 2H),benzamidine 9.43 (s, 1H) 132 N-hydroxy-4-[5-(4-{5- 1.15 (m, 6H), 1.56(m, 2H), 1.78 (brm, DMSO-d₆ ethyl-2-[ethyl-(2- 4H), 2.42 (brm, 4H), 2.51(m, 2H), morpholinoethyl)- 2.70 (q, 2H), 3.40 (m, 2H), 3.48 (m, 2H),amino]-1,3-thiazol-4- 3.53 (brm, 4H), 4.00 (m, 4H), 5.70 (s,yl}phenoxy)pentyloxy]- 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.42 (d,benzamidine 2H), 7.57 (d, 2H), 9.43 (s, 1H) 133 N-hydroxy-4-[5-{4-[2-1.17 (t, 3H), 1.57 (brm, 2H), 1.77 (brm, DMSO-d₆ (benzyl-methyl-amino)-4H), 2.74 (q, 2H), 2.98 (s, 3H), 3.99 (m, 5-ethyl-1,3-thiazol-4- 4H),4.64 (s, 2H), 5.71 (s, 2H), 6.90 (d, yl]phenoxy}pentyloxy]- 2H), 6.94(d, 2H), 7.30 (m, 5H), 7.45 (d, benzamidine 2H), 7.57 (d, 2H), 9.44 (s,1H) 134 N-hydroxy-4-[5-(4-{5- 1.18 (t, 3H), 1.56 (m, 2H), 1.77 (brm,DMSO-d₆ ethyl-2-[methyl- 4H), 2.74 (q, 2H), 3.01 (s, 3H), 3.99 (t,(pyridin-3- 4H), 4.69 (s, 2H), 5.70 (s, 2H), 5.90 (d,ylmethyl)amino]-1,3- 2H), 6.95 (d, 2H), 7.37 (m, 1H), 7.45 (d,thiazol-4- 2H), 7.57 (d, 2H), 7.72 (d, 1H), 8.47 (d,yl}phenoxy)pentyloxy]- 1H), 8.55 (s, 1H), 9.43 (s, 1H) benzamidine 135N-hydroxy-4-(5-{4-[2- 1.15 (m, 6H), 1.56 (m, 2H), 1.76 (brm, DMSO-d₆(benzyl-ethyl-amino)-5- 4H), 2.73 (q, 2H), 3.41 (q, 2H), 3.99 (t,ethyl-1,3-thiazol-4- 4H), 4.63 (s, 2H), 5.70 (s, 2H), 6.90 (d,yl]phenoxy}pentyloxy)- 2H), 6.94 (d, 2H), 7.25 (m, 1H), 7.32 (m,benzamidine 4H) 7.44 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) 136N-hydroxy-4-{5-(4-[5- 1.15 (m, 6H), 1.56 (m, 2H), 1.76 (m, 4H), DMSO-d₆ethyl-2-(ethyl- 2.73 (q, 2H), 3.44 (q, 2H), 3.99 (t, 4H), [pyridin-3-4.66 (s, 2H), 5.70 (s, 2H), 5.74 (s, 1H), ylmethyl]amino)-1,3- 6.90 (d,2H), 6.94 (d, 2H), 7.36 (m, 1H), thiazol-4- 7.43 (d, 2H), 7.57 (d, 2H),7.73 (d, 2H), yl]phenoxy)pentyloxy}- 8.46 (d, 1H), 8.56 (d, 1H), 9.44(s, 1H) benzamidine 137 N-hydroxy-4-[5-(4-{2- 1.15 (t, 3H), 1.56 (brm,2H), 1.79 (brm, DMSO-d₆ [bis-(pyridin-3- 4H), 2.73 (q, 2H), 3.99 (t,2H), 4.09 (t, ylmethyl)amino]-5- 2H), 4.91 (s, 4H), 6.95 (d, 2H), 7.14(d, ethyl-1,3-thiazol-4- 2H), 7.41 (d, 2H), 7.67 (d, 2H), 7.82 (m,yl}phenoxy)pentyloxy]- 2H), 8.26 (m, 2H), 8.73 (m, 2H), 8.79 (s,benzamidine 2H). 138 N-hydroxy-4-{5-[4-(2- 0.86 (t, 6H), 1.17 (t, 3H),1.59 (brm, DMSO-d₆ dipropylamino-5-ethyl- 6H), 1.77 (brm, 4H), 2.71 (q,2H), 1,3-thiazol-4- 3.30 (m, 4H), 3.99 (m, 4H), 5.71 (brs,yl)phenoxy]pentyloxy}- 2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.42 (d,benzamidine 2H), 7.57 (d, 2H), 9.44 (s, 1H) 139 N-hydroxy-4-[5-(4-{2-1.17 (t, 3H), 1.57 (brm, 2H), 1.77 (brm, DMSO-d₆ [bis-(2- 4H), 2.71 (q,2H), 3.48 (m, 4H), 3.63 (m, hydroxyethyl)amino]-5- 4H), 3.99 (m, 4H),4.87 (t, 2H), 5.69 (s, ethyl-1,3-thiazol-4- 2H), 6.90 (d, 2H), 6.94 (d,2H), 7.41 (d, yl}phenoxy)pentyloxy]- 2H), 7.57 (d, 2H), 9.43 (s, 1H)benzamidine 140 N-hydroxy-4-[5-(4-{2- 1.26 (d, 6H), 1.57 (m, 2H), 1.79(m, 4H), DMSO-d₆ [(2-hydroxyethyl)- 3.33 (m, 5H), 3.47 (m, 1H), 3.61 (m,2H), methyl-amino]-5- 4.00 (m, 4H), 5.72 (s, 2H), 6.90~7.00 (b,isopropyl-1,3-thiazol- 4H), 7.45 (d, 2H), 7.57 (d, 2H), 9.45 (s, 4- 1H)yl}phenoxy)pentyloxy]- benzamidine 141 N-hydroxy-4-[5-(4-{5- 1.20 (d,6H), 1.56 (m, 2H), 1.79 (m, 4H), DMSO-d₆ isopropyl-2-[methyl- 3.01 (s,3H), 3.24 (m, 1H), 3.32 (s, 2H), (pyridin-3- 4.00 (m, 4H), 5.70 (s, 2H),6.90 (b, 4H), ylmethyl)amino]-1,3- 7.40 (b, 3H), 7.57 (d, 2H), 7.92 (m,1H), thiazol-4- 8.47~8.56 (b, 2H), 9.43 (s, 1H) yl}phenoxy)pentyloxy]-benzamidine 142 N-hydroxy-4-(5-{4-[2- 1.24 (m, 9H), 1.56 (brm, 2H), 1.79(brm, DMSO-d₆ (ethanesulphonyl- 4H), 3.41 (s, 3H), 3.46 (q, 2H), 4.00(m, methyl-amino)-5- 4H), 5.74 (s, 2H), 6.91 (d, 2H), 6.95 (d,isopropyl-1,3-thiazol- 2H), 7.45 (d, 2H), 7.57 (d, 2H), 9.45 (s, 4- 1H)yl]phenoxy}pentyloxy)- benzamidine 143 N-hydroxy-4-[5-(4-{5- 0.84 (t,3H), 1.32 (m, 2H), 1.54 (m, 4H), DMSO-d₆ butyl-2-[(2- 1.78 (m, 4H), 2.70(t, 2H), 3.303 (s, hydroxyethyl)-methyl- 3H), 3.46 (t, 2H), 3.54 (m,2H), 4.01 (m, amino]-1,3-thiazol-4- 4H), 5.71 (s, 2H), 6.91 (d, 2H),6.94 (d, yl}phenoxy)pentyloxy]- 2H), 7.42 (d, 2H), 7.58 (d, 2H), 9.46(s, benzamidine 1H) 144 N-hydroxy-4-[5-(4-{5- 0.83 (t, 3H), 1.30 (m,2H), 1.53 (m, 4H), DMSO-d₆ butyl-2-[methyl-(2- 1.77 (brm, 4H), 2.42(brm, 4H), 2.52 (m, morpholinoethyl)amino]- 2H), 2.69 (m, 2H), 2.99 (s,3H), 1,3-thiazol-4- 3.52 (brm, 6H), 4.00 (m, 4H), 5.72 (s,yl}phenoxy)pentyloxy]- 2H), 6.92 (m, 4H), 7.41 (d, 2H), 7.57 (d,benzamidine 2H), 9.44 (s, 1H) 145 N-hydroxy-4-[5-(4-{5- 0.82 (t, 3H),1.29 (m, 2H), 1.52 (brm, DMSO-d₆ butyl-2-[methyl- 4H), 1.76 (brm, 4H),2.70 (m, 2H), (pyridin-3- 3.00 (s, 3H), 3.98 (m, 4H), 4.68 (s, 2H),ylmethyl)amino]-1,3- 5.76 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H),thiazol-4- 7.37 (m, 1H), 7.44 (d, 2H), 7.58 (d, 2H),yl}phenoxy)pentyloxy]- 7.72 (d, 1H), 8.47 (d, 1H), 8.55 (s, 1H),benzamidine 9.48 (s, 1H) 146 N-hydroxy-4-{5-[4-(5- 0.84 (m, 9H), 1.30(m, 2H), 1.57 (m, 8H), DMSO-d₆ butyl-2-dipropylamino- 1.77 (brm, 4H),2.68 (m, 2H), 3.33 (m, 1,3-thiazol-4- 4H), 4.00 (m, 4H), 5.70 (s, 2H),6.90 (d, yl)phenoxy]pentyloxy}- 2H), 6.94 (d, 2H), 7.41 (d, 2H), 7.57(d, benzamidine 2H), 9.43 (s, 1H) 147 N-hydroxy-4-[5-(4-{5- 1.10 (m,2H), 1.51 (m, 6H), 1.76 (brm, DMSO-d₆ cyclopentylmethyl-2- 6H), 1.99 (m,1H), 2.71 (d, 2H), 3.00 (s, [methyl-(pyridin-3- 3H), 3.99 (t, 4H), 4.68(s, 2H), 5.72 (s, ylmethyl)amino]-1,3- 2H), 6.90 (d, 2H), 6.95 (d, 2H),7.36 (m, thiazol-4- 1H), 7.43 (d, 2H), 7.57 (d, 2H), 7.72 (d,yl}phenoxy)pentyloxy]- 1H), 8.48 (d, 1H), 8.55 (s, 1H), 9.45 (s,benzamidine 1H) 148 N-hydroxy-4-[5-(4-{5- 1.11 (brm, 2H), 1.52-1.56(brm, 6H), DMSO-d₆ cyclopentylmethyl-2- 1.77 (brm, 6H), 2.0 (m, 1H),2.69 (m, [methyl-(2- 2H), 3.00 (s, 3H), 3.33 (m, 4H), 3.55 (m,morpholinoethyl)amino]- 6H), 4.00 (m, 4H), 5.81 (s, 2H), 6.93 (m,1,3-thiazol-4- 4H), 7.40 (d, 2H), 7.57 (d, 2H), 9.50 (s,yl}phenoxy)pentyloxy]- 1H) benzamidine 149 N-hydroxy-4-{5-[4-(5- 0.85(m, 6H), 1.08 (m, 2H), DMSO-d₆ cyclopentylmethyl-2- 1.46-1.77 (brm,16H), 1.99 (m, 1H), 2.67 (d, 2H), dipropylamino-1,3- 3.30 (m, 4H), 3.99(m, 4H), 6.04 (s, 2H), thiazol-4- 6.90 (d, 2H), 6.93 (d, 2H), 7.41 (d,2H), yl)phenoxy]pentyloxy}- 7.59 (d, 2H), 9.60 (s, 1H) benzamidine 150N-hydroxy-4-{5-[4-(5- 0.84 (m, 3H), 1.14 (t, 6H), 1.30 (m, 2H), DMSO-d₆butyl-2-diethylamino- 1.55 (m, 4H), 1.77 (m, 4H), 2.69 (m, 2H),1,3-thiazol-4- 3.40 (m, 4H), 3.98 (m, 4H), 5.73 (s, 2H),yl)phenoxy]pentyloxy}- 6.92 (d-d, 4H), 7.43 (d, 2H), 7.60 (d,benzamidine 2H), 9.49 (s, 1H) 151 N-hydroxy-4-{5-[4-(5- 0.85 (t, 3H),1.12 (t, 3H), 1.30 (m, 2H), DMSO-d₆ butyl-2- 1.53 (m, 4H), 1.78 (m, 4H),2.70 (m, 2H), ethylmethylamino-1,3- 2.96 (s, 3H), 3.42 (m, 2H), 5.74 (s,2H), thiazol-4- 6.93 (m, 4H), 7.43d, 2H), 7.59 (d, 2H),yl)phenoxy]pentyloxy}- 9.47 (s, 1H) benzamidine 152N-hydroxy-4-{5-[4-(5- 0.81 (t, 3H), 1.25 (m, 2H), 1.52 (m, 4H), DMSO-d₆butyl-2-dimethylamino- 1.76 (m, 4H), 2.67 (m, 2H), 2.97 (s, 6H),1,3-thiazol-4- 3.97 (m, 4H), 5.70 (s, 2H), 6.91 (d-d,yl)phenoxy]pentyloxy}- 4H), 7.41 (d, 2H), 7.57 (d, 2H), 9.50 (s,benzamidine 1H) 153 N-hydroxy-4-[5-(4-{5- 1.56-1.59 (m, 6H), 1.73-1.81(m, 6H), DMSO-d₆ cyclopentyl-2-[methyl- 2.00-2.10 (m, 2H), 2.38-2.49 (m,4H), (2- 2.50-2.51 (m, 2H), 3.01 (s, 3H), 3.25 (m,morpholinoethyl)amino]- 1H), 3.52--3.55 (m, 6H), 4.00-4.03 (m,1,3-thiazol-4- 4H), 5.74 (s, 2H), 6.91-6.97 (m, 4H),yl}phenoxy)pentyloxy]- 7.41 (d, 2H), 7.59 (d, 2H), 9.47 (s, 1H)benzamidine 154 N-hydroxy-4-[5-(4-{5- 0.88 (d, 6H), 1.78 (m, 2H),1.80-1.82 (m, DMSO-d₆ isobutyl-2-[methyl-(2- 5H), 2.43 (s, 3H), 2.50 (m,2H), 2.53 (m, morpholinoethyl)amino]- 2H), 3.01 (m, 2H), 3.18 (m, 2H),3.54 (m, 1,3-thiazol-4- 6H), 4.02 (m, 4H), 5.76 (s, 2H),yl}phenoxy)pentyloxy]- 6.94-6.97 (m, 4H), 7.41 (d, 2H), 7.60 (d, 2H),benzamidine 9.46 (s, 1H) 155 N-hydroxy-4-(5-{4-[5- 1.58-1.66 (m, 2H),1.78-1.81 (m, 4H), DMSO-d₆ (2-chloroehtyl)-2- 3.14 (s, 6H), 3.15 (t,2H), 3.81 (t, 2H), dimethylamino-1,3- 4.02 (m, 4H), 5.72 (s, 2H),6.91-6.98 (m, thiazol-4- 4H), 7.46 (d, 2H), 7.59 (d, 2H), 9.45 (s,yl]phenoxy}pentyloxy)- 1H) benzamidine 156 N-hydroxy-4-{5-[4-(5-0.86-0.88 (m, 6H), 1.58-1.61 (m, 10H), DMSO-d₆ cyclopentyl-2- 1.78 (m,8H), 3.32-3.39 (m, 5H), diethylamino-1,3- 4.02-4.05 (m, 4H), 6.95-7.18(m, 4H), 7.40 (d, thiazol-4- 2H), 7.83 (d, 2H) yl)phenoxy]pentyloxy}-benzamidine 157 N-hydroxy-4-{5-[4-(5- 0.84-0.88 (m, 6H), 1.24 (d, 6H),DMSO-d₆ isopropyl-2- 1.57-1.63 (m, 6H), 1.77-1.79 (m, 4H),dipropylamino-1,3- 3.28-3.38 (m, 5H), 3.97-4.01 (m, 4H), 5.71 (s,thiazol-4- 2H), 6.89-6.95 (m, 4H), 7.41-4.59 (m, yl)phenoxy]pentyloxy}-4H), 9.45 (s, 1H) benzamidine 158 N-hydroxy-4-{5-[4-(5- 1.15 (t, 3H),1.23 (t, 6H), 1.58 (m, 2H), DMSO-d₆ ethyl-2-diethylamino- 1.79-1.83 (m,4H), 2.51 (m, 2H), 1,3-thiazol-4- 3.60-3.64 (m, 4H), 4.08-4.12 (m, 4H),yl)phenoxy]pentyloxy}- 7.13-7.16 (m, 4H), 7.43 (d, 2H), 7.69 (d, 2H)benzamidine 159 N-hydroxy-4-[5-(4-{5- 1.22 (d, 6H), 1.56 (m, 2H), 1.78(m, 4H), DMSO-d₆ isopropyl-2-[methyl-(2- 2.43 (m, 4H), 2.55 (t, 2H),3.05 (s, 3H), morpholinoethyl)amino]- 3.34 (m, 1H), 3.51 (m, 4H), 3.61(t, 2H), 1,3-thiazol-4- 3.99 (m, 4H), 5.70 (brs, 2H), 6.90 (m,yl}phenoxy)pentyloxy]- 4H), 7.57 (m, 2H), 7.73 (m, 2H), benzamidine 9.44(brs, 1H) 160 N-hydroxy-4-{5-[4-(5- 1.12-1.16 (m, 8H), 1.56 (m, 6H),1.78 (m, DMSO-d₆ cyclopentylmethyl-2- 6H), 1.98-2.00 (m, 1H), 2.68 (d,2H), diethylamino-1,3- 3.38-3.40 (m, 4H), 4.00 (m, 4H), 5.89 (s,thiazol-4- 2H), 6.91-6.95 (d-d, 4H), 7.42 (d, 2H),yl)phenoxy]pentyloxy}- 7.59 (d, 2H), 9.53 (s, 1H) benzamidine 161N-hydroxy-4-{5-[4-(5- 1.20 (d, 6H), 1.56 (m, 2H), 1.78 (m, 4H), DMSO-d₆isopropyl-2- 2.98 (s, 6H), 3.34 (m, 1H), 3.98-4.01 (m,dimethylamino-1,3- 4H), 5.77 (s, 2H), 6.90-6.96 (m, 4H), thiazol-4- 7.39(d, 2H), 7.58 (d, 2H), 9.47 (s, 1H) yl)phenoxy]pentyloxy}- benzamidine162 N-hydroxy-4-{5-[4-(5- 1.14 (m, 6H), 1.20 (d, 6H), 1.56 (m, 2H),DMSO-d₆ isopropyl-2- 1.78 (m, 4H), 3.30 (m, 1H), 3.40 (m, 4H),diethylamino-1,3- 5.84 (s, 2H), 6.91-7.59 (m, 8H), 9.51 (s, thiazol-4-1H) yl)phenoxy]pentyloxy}- benzamidine 163 N-hydroxy-4-{5-[4-(5-1.10-1.18 (m, 2H), 1.44-1.57 (m, 6H), DMSO-d₆ cyclopentylmethyl-2-1.70-1.79 (m, 6H), 1.98-2.01 (m, 1H), dimethylamino-1,3- 2.69 (d, 2H),2.98 (s, 6H), 3.97-4.02 (m, thiazol-4- 4H), 5.77 (s, 2H), 6.90-6.94(d-d, 4H), yl)phenoxy]pentyloxy}- 7.42 (d, 2H), 7.59 (d, 2H), 9.48 (s,1H) benzamidine 164 N-hydroxy-4-{5-[4-(5- 1.56 (m, 2H), 1.63 (brm, 6H),1.78 (brm, DMSD-d₆ + methyl-2-piperidino- 4H), 3.60 (brm, 4H), 4.02 (t,2H), TFA-d₁ 1,3-thiazol-4- 4.06 (t, 2H), 7.04 (d, 2H), 7.09 (d, 2H),yl)phenoxy]pentyloxy}- 7.40 (d, 2H), 7.66 (d, 2H) benzamidine 165N-hydroxy-4-{5-[4-(5- 1.56 (m, 2H), 1.78 (brm, 4H), 2.21 (s, DMSD-d₆ +methyl-2-morpholino- 3H), 3.60 (brm, 4H), 3.74 (brm, 4H), TFA-d₁1,3-thiazol-4- 4.02 (t, 2H), 4.05 (t, 2H), 7.03 (d, 2H),yl)phenoxy]pentyloxy}- 7.09 (d, 2H), 7.40 (d, 2H), 7.65 (d, 2H)benzamidine 166 N-hydroxy-4-{5-[4-(5- 1.09 (t, 3H), 1.55 (m, 2H), 1.61(brm, DMSD-d₆ + ethyl-2-piperidino-1,3- 6H), 1.77 (brm, 4H), 2.56 (q,2H), TFA-d₁ thiazol-4- 3.59 (brm, 4H), 4.00 (t, 2H), 4.03 (t,yl)phenoxy]pentyloxy}- 2H), 7.01 (d, 2H), 7.06 (d, 2H), 7.34 (d,benzamidine 2H), 7.64 (d, 2H) 167 N-hydroxy-4-{5-[4-(5- 1.01 (brm, 2H),1.43 (brm, 4H), DMSD-d₆ + cyclopentylmethyl-2- 1.56 (brm, 2H), 1.63(brm, 8H), TFA-d₁ piperidino-1,3-thiazol- 1.78 (brm, 4H), 1.94 (m, 1H),2.56 (d, 4- 2H), 3.61 (brm, 4H), 4.05 (m, 4H), yl)phenoxy]pentyloxy}-7.04 (d, 2H), 7.10 (d, 2H), 7.36 (d, 2H), benzamidine 7.66 (d, 2H) 168N-hydroxy-4-{5-[4-(5- 1.02 (brm, 2H), 1.43 (brm, 4H), DMSD-d₆ +cyclopentylmethyl-2- 1.56 (brm, 2H), 1.66 (brm, 2H), TFA-d₁morpholino-1,3-thiazol- 1.78 (brm, 4H), 1.94 (m, 1H), 2.58 (d, 4- 2H),3.61 (brm, 4H), 3.74 (brm, 4H), yl)phenoxy]pentyloxy}- 4.05 (m, 4H),7.04 (d, 2H), 7.09 (d, 2H), benzamidine 7.36 (d, 2H), 7.65 (d, 2H) 169N-hydroxy-4-{5-[4-(5- 1.22 (d, 6H), 1.58 (m, 2H), 1.78 (m, 4H), DMSO-d₆isopropyl-2-morpholino- 3.26 (m, 1H), 3.35 (m, 4H), 3.70 (m,1,3-thiazol-4- 4H), 4.02 (m, 4H), 5.71 (brs, 2H), yl)phenoxy]pentyloxy}-6.95 (m, 4H), 7.40 (d, 2H), 7.58 (d, 2H), benzamidine 9.44 (s, 1H) 170N-hydroxy-4-{5-(4-[5- 1.11 (brm, 2H), 1.52-1.56 (brm, 6H), DMSO-d₆cyclopentylmethyl-2-(4- 1.77 (brm, 6H), 2.00 (m, 1H), 2.50 (m,methylpiperazino)-1,3- 2H), 2.69 (m, 2H), 3.00 (s, 3H), 3.33 (m,thiazol-4- 4H), 3.55 (m, 6H), 4.00 (m, 4H), yl]phenoxy)pentyloxy}- 5.81(brs, 2H), 6.93 (m, 4H), 7.40 (d, benzamidine 2H), 7.57 (d, 2H), 9.50(brs, 1H) 171 N-hydroxy-4-{5-[4-(5- 1.55 (m, 2H), 1.79 (m, 4H), 3.17 (d,1H), DMSO-d₆ vinyl-2-morpholin-4-yl- 3.35 (m, 4H), 3.42 (m, 2H), 3.72(m, 4H), 1,3-thiazol-4- 4.01 (m, 4H), 5.74 (s, 2H), 6.92 (m, 4H),yl)phenoxy]pentyloxy}- 7.60 (d, 2H), 7.77 (d, 2H), 9.45 (s, 1H)benzamidine 172 N-hydroxy-4-{5-[4-(5- 1.58-1.60 (m, 7H), 1.74-1.81 (m,7H), DMSO-d₆ cyclopentyl-2- 2.51 (m, 4H), 3.34-3.36 (m, 1H),morpholin-4-yl-1,3- 3.69-3.71 (m, 4H), 4.00-4.02 (m, 4H), 5.77 (s,thiazol-4- 2H), 6.92-6.98 (m, 4H), 7.42 (d, 2H), yl)phenoxy]pentyloxy}-7.59 (d, 2H), 9.48 (s, 1H) benzamidine 173 N-hydroxy-4-{5-[4-(5- 0.88(d, 6H), 1.59 (m, 2H), 1.80 (m, 4H), DMSO-d₆ isobutyl-2-morpholin-4-2.60 (m, 1H), 3.35 (m, 8H), 3.70 (m, 2H), yl-1,3-thiazol-4- 4.01 (m,4H), 5.77 (brs, 2H), 6.94 (m, yl)phenoxy]pentyloxy}- 4H), 7.44 (m, 2H),7.59 (m, 2H), benzamidine 9.48 (brs, 1H) 174 N-hydroxy-4-{5-(4-[5- 1.19(t, 3H), 1.50-1.59 (m, 2H), 1.80 (m, DMSO-d₆ ethyl-2-(4- 4H), 2.21 (s,3H), 2.41 (m, 4H), 3.36 (m, methylpiperazino)-1,3- 6H), 4.01 (m, 4H),5.71 (brs, 2H), thiazol-4- 6.93-6.96 (m, 4H), 7.44 (m, 2H), 7.58 (m,2H), yl]phenoxy)pentyloxy}- 9.46 (brs, 1H) benzamidine 175N-hydroxy-4-{5-[4-(2- 1.56 (m, 2H), 1.77 (m, 4H), 3.42 (m, 8H), DMSO-d₆morpholin-4-yl-1,3- 3.98 (m, 4H), 5.73 (brs, 2H), 6.81 (m, thiazol-4-2H), 6.92 (m, 2H), 7.11 (s, 1H), 7.27 (m, yl)phenoxy]pentyloxy}- 2H),7.77 (m, 2H), 8.35 (brs, 1H) benzamidine 176 N-hydroxy-4-{5-(4-[5- 1.23(d, 6H), 1.58 (m, 2H), 1.77 (m, 4H), DMSO-d₆ isopropyl-2-(4- 2.21 (s,3H), 2.40 (m, 4H), 2.21 (s, 3H), methylpiperazino)-1,3- 2.40 (m, 4H),3.33 (m, 1H), 3.35 (m, 4H), thiazol-4- 4.00 (m, 4H), 5.71 (s, 2H),6.93-6.97 (m, yl]phenoxy)pentyloxy}- 4H), 7.40 (d, 2H), 7.58 (d, 2H),9.45 (s, benzamidine 1H) 177 N-hydroxy-4-{5-[4-(5- 1.23 (d, 6H), 1.52(m, 2H), 1.60 (m, 2H), DMSO-d₆ isopropyl-2-methyl-1,3- 1.75 (m, 2H),2.60 (s, 3H), 3.03 (m, 2H), thiazol-4-yl)-phenoxy]- 3.32 (m, 1H), 4.00(t, 2H), 5.52 (s, 2H), pentylamino}- 5.79 (m, 1H), 6.51 (d, 2H), 6.99(d, 2H), benzamidine 7.37 (d, 2H), 7.42 (d, 2H), 9.19 (s, 1H) 178N-hydroxy-4-(2-{2-[4- 1.25 (d, 6H), 2.64 (s, 3H), 3.33 (m, 1H), CDCl₃(5-isopropyl-2-methyl- 3.90 (m, 4H), 4.14 (m, 4H), 6.90 (m, 4H),1,3-thiazol-4-yl)- 7.40 (m, 4H) phenoxy]-ethoxy}- ethoxy)-benzamidine179 N-hydroxy-4-{3-hydroxy- 1.26 (d, 6H), 1.32 (s, 3H), 2.06 (m, 4H),CDCl₃ 5-[4-(5-isopropyl-2- 2.65 (s, 3H), 3.33 (m, 1H), 4.20 (m, 4H),methyl-1,3-thiazol-4- 5.01 (brs, 1H), 6.86 (d, 2H), 6.92 (d,yl)-phenoxy]-3-methyl- 2H), 7.43 (d, 2H), 7.50 (d, 2H)pentyloxy}-benzamidine 180 N-hydroxy-4-(2-{2-[4- 1.10 (d, 3H), 1.23 (d,6H), 2.59 (s, 3H), DMSO-d₆ (5-isopropyl-2-methyl- 2.96 (m, 2H), 3.05 (m,1H), 3.32 (m, 2H), 1,3-thiazol-4-yl)- 3.90 (m, 2H), 4.04 (m, 2H), 5.71(s, 2H), phenoxy]-1-methyl- 6.92 (d, 2H), 6.99 (d, 2H), 7.43 (d, 2H),ethylamino}-ethoxy)- 7.58 (d, 2H), 9.45 (s, 1H) benzamidine 181N-hydroxy-4-[3-(4-{3- 1.23 (d, 6H), 1.85 (m, 4H), 2.40 (brm, DMSO-d₆[4-(5-isopropyl-2- 12H), 2.45 (s, 3H), 3.30 (m, 1H),methyl-1,3-thiazol-4- 4.00 (m, 4H), 5.70 (s, 2H), 6.89 (d, 2H),yl)-phenoxy]-propyl}- 6.94 (d, 2H), 7.41 (d, 2H), 7.57 (d, 2H),piperazine-1-yl)- 9.51 (s, 1H) propoxy]-benzamidine 182N-hydroxy-4-5-[4-(5- 1.23 (d, 6H), 1.77 (brs, 4H), 2.40 (m, DMSO-d₆isopropyl-2-methyl-1,3- 2H), 2.60 (s, 3H), 3.33 (m, 1H),thiazol-4-yl)-phenoxy]- 4.02 (brs, 2H), 5.72 (s, 2H), 6.99 (d,pentanoyl-amino- 2H), 7.43 (d, 2H), 7.58-7.80 (m, 4H), benzamidine 9.51(s, 1H), 10.00 (s, 1H) 183 N-hydroxy-4-({5-[4-(5- 1.22 (d, 6H), 1.43 (m,2H), 1.55 (m, 2H), DMSO-d₆ isopropyl-2-methyl-1,3- 1.76 (m, 2H), 2.59(s, 3H), 2.89 (s, 3H), thiazol-4-yl)-phenoxy]- 3.33 (m, 1H), 3.98 (m,2H), 5.55 (s, 2H), pentyl}-methyl-amino)- 6.64 (d, 2H), 6.97 (d, 2H),7.45 (m, 4H), benzamidine 9.23 (s, 1H) 184 N-hydroxy-4-{4-[4-(5- 1.23(d, 6H), 2.60 (s, 3H), 3.31 (m, 1H), DMSO-d₆ isopropyl-2-methyl-1,3-4.63 (brs, 4H), 5.73 (s, 2H), 6.08 (brs, thiazol-4-yl)-phenoxy]- 2H),6.94 (d, 2H), 7.01 (d, 2H), 7.44 (d, but-2-enyloxy}- 2H), 7.58 (d, 2H),9.46 (s, 1H) benzamidine 185 N-hydroxy-4-{4-[4-(5- 1.23 (d, 6H), 2.64(s, 3H), 3.32 (m, 1H), DMSO-d₆ isopropyl-2-methyl-1,3- 5.15 (s, 2H),5.23 (s, 2H), 5.72 (s, 2H), thiazol-4-yl)- 7.07 (d, 2H), 7.19 (d, 2H),7.46 (m, 6H), phenoxymethyl]- 7.73 (d, 2H), 9.46 (s, 1H)benzyloxy}-benzamidine 186 N-hydroxy-4-(2-{2-[4- 1.23 (d, 6H), 2.59 (s,3H), 3.01 (brs, DMSO-d₆ (5-isopropyl-2-methyl- 4H), 3.33 (m, 1H), 4.09(m, 4H), 5.71 (s, 1,3-thiazol-4- 2H), 6.92 (d, 2H), 7.00 (d, 2H), 7.43(d, yl)phenoxy]- 2H), 7.58 (d, 2H), 9.45 (s, 1H) ethylamino}-ethoxy)-benzamidine 187 N-hydroxy-2-fluoro-4- 1.23 (d, 6H), 1.57 (m, 2H), 1.79(m, 4H), DMSO-d₆ {5-[4-(5-isopropyl-2- 2.49 (s, 3H), 3.33 (m, 1H), 4.02(m, 4H), methyl-1,3-thiazol-4- 5.70 (s, 2H), 6.83 (m, 2H), 6.98 (d, 2H),yl)-phenoxy]- 7.43 (m, 3H), 9.51 (s, 1H) pentyloxy}-benzamidine 1882,N-dihydroxy-4-{5-[4- 1.23 (d, 6H), 1.56 (m, 2H), 1.77 (m, 4H), DMSO-d₆(5-isopropyl-2-methyl- 2.60 (s, 3H), 3.32 (m, 1H), 4.00 (m, 4H),1,3-thiazol-4-yl)- 6.25 (s, 2H), 6.36 (m, 2H), 7.00 (d, 2H),phenoxy]-pentyloxy}- 7.42 (d, 2H), 7.52 (d, 1H), 9.81 (s, 1H),benzamidine 12.40 (s, 1H) 189 N-hydroxy-4-{5-[4-(5- 1.24 (d, 6H), 1.58(m, 2H), 1.80 (m, 4H), DMSO-d₆ isopropyl-2-methyl-1,3- 2.61 (s, 3H),3.35 (m, 1H), 3.77 (s, 3H) thiazol-4-yl)-phenoxy]- 4.02 (m, 4H), 5.77(s, 2H), 6.98 (m, 3H), pentyloxy}-3-methoxy- 7.26 (m, 2H), 7.46 (d, 2H),9.48 (s, 1H) benzamidine 190 N-hydroxy-2- 1.23 (m, 12H), 1.54 (m, 2H),1.65 (m, DMSO-d₆ cyclohexylamino-4-{5- 2H), 1.76 (m, 4H), 1.78 (m, 2H),2.60 (s, [4-(5-isopropyl-2- 3H), 3.34 (m, 2H), 3.99 (m, 4H), 5.66 (s,methyl-1,3-thiazol-4- 2H), 6.09 (m, 2H), 6.97 (d, 2H), 7.31 (d,yl)-phenoxy]- 1H), 7.43 (d, 2H), 7.70 (d, 1H), 9.48 (s,pentyloxy}-benzamidine 1H) 191 N-hydroxy-4-{5-[3- 1.17 (d, 6H), 1.57 (m,2H), 1.79 (brs, DMSO-d₆ fluoro-4-(5-isopropyl- 4H), 2.98 (m, 1H), 4.04(m, 4H), 5.71 (s, 2-methyl-1,3-thiazol-4- 2H), 6.90 (m, 3H), 7.31 (d,2H), 7.59 (d, yl)-phenoxy]- 2H), 9.44 (s, 1H) pentyloxy}-benzamidine 192N-hydroxy-2-fluoro-4- 1.17 (d, 6H), 1.57 (brs, 2H), 1.79 (brs, DMSO-d₆{5-[3-fluoro-4-(5- 4H), 2.98 (m, 1H), 4.05 (m, 4H), 5.73 (s,isopropyl-2-methyl-1,3- 2H), 6.82~6.89 (m, 4H), 7.27~7.40 (m,thiazol-4-yl)-phenoxy]- 2H), 9.52 (s, 1H) pentyloxy}-benzamidine 193N-hydroxy-4-{3-[4-(5- 1.24 (d, 6H), 2.20 (m, 2H), 2.60 (s, 3H), DMSO-d₆isopropyl-2-methyl-1,3- 3.30 (m, 1H), 4.17 (m, 4H), 5.71 (s, 2H),thiazol-4- 6.96 (d, 2H), 7.01 (d, 2H), 7.44 (d, 2H),yl)phenoxy]propoxy}- 7.60 (d, 2H), 9.45 (s, 1H) benzamidine 194N-hydroxy-4-{4-[4-(5- 1.26 (d, 2H), 1.89 (m, 4H), 2.60 (s, 3H), DMSO-d₆isopropyl-2-methyl-1,3- 3.30 (m, 1H), 4.06 (m, 4H), 5.72 (s, 2H),thiazol-4- 6.92 (d, 2H), 7.00 (d, 2H), 7.44 (d, 2H), yl)phenoxy]butoxy}-7.60 (d, 2H), 9.45 (s, 1H) benzamidine 195 N-hydroxy-3-{5-[4-(5- 1.24(d, 6H), 1.50-1.62 (m, 3H), DMSO-d₆ isopropyl-2-methyl- 1.77-1.79 (m,2H), 2.65 (s, 3H), 3.02-3.04 (m, thiazol-4-yl)-phenoxy]- 1H), 3.37-3.44(m, 3H), 3.99-4.03 (m, pentylamino}- 2H), 6.57-6.98 (m, 4H), 7.00 (d,2H), benzamidine 7.44 (d, 2H) 196 N-hydroxy-4-{4-[4-(2- 1.22 (t, 3H),1.39-1.44 (m, 3H), 1.59 (m, DMSO-d₆ cyclohexyl-5-ethyl- 1H), 1.77 (m,2H), 1.89 (m, 4H), 2.03 (m, thiazol-4-yl)-phenoxy]- 2H), 2.90 (m, 3H),4.18 (m, 4H), 7.00 (m, butoxy}-benzamidine 4H), 7.49 (m, 2H), 7.60 (m,2H) 197 N-hydroxy-4-[3-(4-{5- 1.17 (m, 3H), 2.19 (m, 2H), 2.72 (m, 2H),DMSO-d₆ ethyl-2-[(2- 3.05 (s, 3H), 3.39-3.79 (m, 4H),hydroxyethyl)-methyl- 4.16-4.20 (m, 4H), 5.72 (s, 2H), 6.96 (m, 4H),amino]-thiazol-4- 7.40-7.84 (m, 4H), 9.47 (s, 1H) yl}phenoxy)propoxy]-benzamidine 198 N-hydroxy-4-[4-(4-{5- 1.15 (t, 3H), 1.90 (m, 4H), 2.64(q, 2H), DMSO-d₆ ethyl-2-[(2- 3.25 (s, 3H), 3.40-3.80 (m, 4H),hydroxyethyl)-methyl- 4.10-4.15 (m, 4H), 7.09-7.15 (m, 4H), 7.42 (d,amino]-thiazol-4- 2H), 7.73 (d, 2H) yl}phenoxy)butoxy]- benzamidine 199N-hydroxy-4-[5-(4-{5- 1.86 (t, 3H), 2.50 (m, 2H), 2.73 (m, 2H), DMSO-d₆ethyl-2-[methyl- 3.15 (s, 3H), 4.17-4.25 (m, 4H), 4.96 (s, (pyridin-3-2H), 7.01 (d, 2H), 7.17 (d, 2H), 7.44 (d, ylmethyl)amino]- 2H), 7.73 (d,2H), 8.06 (m, 1H), 8.54 (d, thiazol-4- 1H), 8.87 (d, 1H), 8.94 (s, 1H)yl}phenoxy)propoxy]- benzamidine 200 N-hydroxy-4-[5-(4-{5- 1.19 (t, 3H),1.79-1.89 (m, 4H), DMSO-d₆ ethyl-2-[methyl- 2.72-2.74 (m, 2H), 3.17 (s,3H), 4.07-4.15 (m, (pyridin-3- 4H), 4.98 (s, 2H), 7.00 (d, 2H), 7.14 (d,ylmethyl)amino]- 2H), 7.44 (d, 2H), 7.72 (d, 2H), 8.05 (m, thiazol-4-1H), 8.55 (d, 1H), 8.87 (d, 1H), 8.95 (s, yl}phenoxy)butoxy]- 1H)benzamidine 201 N-hydroxy-4-{4-[4-(5- 1.14 (m, 2H), 1.32 (d, 6H), 1.48(m, 4H), DMSO-d₆ cyclopentylmethyl-2- 1.74 (m, 2H), 2.04 (m, 1H), 2.85(d, 2H), isopropyl-thiazol-4- 3.38 (m, 1H), 5.14 (s, 4H), 5.73 (s, 2H),yl)-phenoxymethyl]- 7.01 (d, 2H), 7.08 (d, 2H), 7.48 (s, 4H),benzyloxy}-benzamidine 7.50 (d, 2H), 7.58 (d, 2H), 9.48 (s, 1H) 202N-hydroxy-4-{4-[4-(5- 0.85 (t, 3H), 1.32 (d, 6H), 1.35 (m, 2H), DMSO-d₆butyl-2-isopropyl- 1.60 (m, 2H), 1.85 (m, 2H), 3.25 (m, 1H),thiazol-4-yl)- 5.15 (s, 4H), 5.74 (s, 2H), 7.01 (d, 2H), phenoxymethyl]-7.08 (d, 2H), 7.48 (s, 4H), 7.50 (d, 2H), benzyloxy}-benzamidine 7.60(d, 2H), 9.49 (s, 1H) 203 N-hydroxy-4-{4-[4-(5- 1.07-1.09 (m, 2H),1.47-1.50 (m, 4H), DMSO-d₆ cyclopentylmethyl-2- 1.70 (m, 2H), 1.99 (m,1H), 2.34 (s, 6H), amino-thiazol-4-yl)- 2.62 (d, 2H), 5.18 (s, 2H), 5.25(s, 2H), phenoxymethyl]- 7.17-7.24 (m, 4H), 7.41 (d, 2H), 7.50 (m,benzyloxy}-benzamidine 4H), 7.68 (d, 2H) 204 N-hydroxy-4-{4-[4-(5- 1.05(m, 2H), 1.49 (m, 4H), 1.71 (m, 2H), DMSO-d₆ cyclopentylmethyl-2- 2.00(m, 1H), 2.34 (s, 6H), 2.63 (d, 2H), amino-thiazol-4-yl)- 5.15-5.26 (d,4H), 7.05-7.24 (m, 3H), phenoxymethyl]- 7.41-7.62 (m, 8H)benzyloxy}-2-fluoro- benzamidine 205 N-hydroxy-4-{4-[4-(2- 2.86 (s, 3H),5.16 (m, 4H), 6.00 (brs, DMSO-d₆ methylamino-thiazol-4- 2H), 7.02 (m,4H), 7.48 (m, 4H), 7.60 (s, yl)-phenoxymethyl]- 1H), 7.76 (m, 4H), 9.57(brs, 1H) benzyloxy}-benzamidine 206 N-hydroxy-4-{6-[4-(5- 1.26 (d, 6H),2.61 (s, 3H), 3.35 (m, 1H), DMSO-d₆ isopropyl-2-methyl- 5.25 (m, 4H),5.75 (brs, 2H), 7.11 (m, thiazol-4-yl)- 1H), 7.13 (m, 2H), 7.47 (m, 4H),7.49 (m, phenoxymethyl]- 2H), 7.80-7.90 (m, 2H), 9.49 (brs, 1H)pyridine-2-yl-methoxy}- benzamidine 207 N-hydroxy-2-fluoro-4- 1.25 (d,6H), 1.89 (m, 4H), 2.61 (s, 3H), DMSO-d₆ {4-[4-(5-isopropyl-2- 3.34 (m,1H), 4.10 (m, 4H), 6.80-6.90 (m, methyl-thiazol-4-yl)- 2H), 7.02 (m,2H), 7.46 (m, 3H) phenoxy]-butoxy}- benzamidine 208N-hydroxy-4-{2-[4-(5- 1.23 (d, 6H), 2.60 (s, 3H), 3.33 (m, 1H), DMSO-d₆isopropyl-2-methyl- 5.28 (s, 4H), 5.80 (s, 2H), 7.04-7.12 (m,thiazol-4-yl)- 4H), 7.37 (m, 2H), 7.47 (d, 2H), 7.55 (m, phenoxymethyl]-2H), 7.64 (d, 2H), 9.57 (s, 1H) benzyloxy}-benzamidine 209N-hydroxy-4-{3-[4-(5- 1.23 (d, 6H), 2.60 (s, 3H), 3.31 (m, 1H), DMSO-d₆isopropyl-2-methyl- 5.14 (s, 2H), 5.15 (s, 2H), 5.72 (s, 2H),thiazol-4-yl)- 7.00 (d, 2H), 7.08 (d, 2H), 7.42-7.46 (m, phenoxymethyl]-5H), 7.55-7.61 (m, 3H), 9.46 (s, 1H) benzyloxy}-benzamidine 210N-hydroxy-4-{4-[4-(5- 1.10 (m, 2H), 1.23 (m, 1H), 1.46 (br, DMSO-d₆cyclopentylmethyl-2- 9H), 1.77 (br, 4H), 2.02 (m, 3H),cyclohexyl-thiazol-4- 2.83 (d, 2H), 2.90 (m, 1H), 5.16 (m, 4H),yl)-phenoxymethyl]- 5.81 (brs, 2H), 7.02 (m, 4H), 7.48 (m,benzyloxy}-benzamidine 4H), 7.76 (m, 4H), 9.57 (brs, 1H) 211N-hydroxy-4-{6-[4-(5- 1.24 (d, 6H), 1.49 (m, 4H), 1.76 (m, 4H), DMSO-d₆isopropyl-2-methyl- 2.61 (s, 3H), 3.32-3.37 (m, 1H),thiazol-4-yl)phenoxy]- 3.99-4.02 (m, 4H), 5.81 (s, 2H), 6.91 (d, 2H),hexyloxy}-benzamidine 6.99 (d, 2H), 7.44 (d, 2H), 7.59 (d, 2H), 9.49 (s,1H) 212 N-hydroxy-4-{5-[2- 1.13 (t, 3H), 1.61 (m, 2H), 1.81 (m, 4H),DMSO-d₆ ethyl-5-hydroxy-4-(2- 2.51 (m, 2H), 2.79 (s, 3H), 3.97-4.10 (m,methyl-thiazol-4- 4H), 6.60 (s, 1H), 7.12 (d, 2H),yl)phenoxy]-pentyloxy}- 7.69-7.86 (m, 4H), 8.81 (s, 1H), 9.26 (s, 1H)benzamidine 213 N-hydroxy-4-{5-[2- 1.03 (t, 3H), 1.13 (t, 3H), 1.62 (m,2H), DMSO-d₆ ethyl-4-(2-methyl- 1.79-1.85 (m, 6H), 2.55 (m, 2H), 2.69(s, thiazol-4-yl)-5- 3H), 4.01-4.08 (m, 6H), 5.73 (s, 2H),propoxy-phenoxy]- 6.67 (s, 1H), 6.92 (d, 2H), 7.59-7.93 (m,pentyloxy}-benzamidine 4H), 9.47 (s, 1H) 214 N-hydroxy-4-(5-{4-[5- 0.86(d, 6H), 1.59 (m, 2H), 1.80 (m, 5H), DMSO-d₆ (2-isobutylamino- 2.60 (s,3H), 2.73 (m, 2H), 2.94 (m, 2H), ethyl)-2-methyl- 3.34 (m, 2H), 4.02 (m,4H), 5.72 (s, 2H), thiazol-4-yl]-phenoxy}- 6.93 (m, 4H), 7.49-7.60 (m,4H), pentyloxy)-benzamidine 9.45 (s, 2H) 215 4-(5-{4-[5-(2- 0.85 (d,6H), 1.58 (m, 2H), 1.79 (m, 5H), DMSO-d₆ isobutylaminoethyl)-2- 2.59 (s,3H), 2.71 (m, 2H), 2.92 (m, 2H), methyl-thiazol-4-yl]- 3.32 (m, 2H),4.01 (m, 4H), 6.93 (m, 4H), phenoxy}-pentyloxy)- 7.57 (m, 4H), 9.09(brs, 3H) benzamidine 216 N-hydroxy-4-(5-{4-[2- 1.52 (m, 2H), 1.58 (m,6H), 1.79 (m, 4H), DMSO-d₆ methyl-5-(2-piperidin- 2.50 (d, 2H), 2.60 (s,3H), 2.98 (d, 2H), 1-yl-ethyl)-thiazol-4- 3.38 (m, 4H), 4.02 (m, 4H),5.73 (s, 2H), yl]-phenoxy}- 6.93-7.00 (m, 4H), 7.48-7.60 (m, 4H),pentyloxy)-benzamidine 9.46 (s, 1H) 217 N-hydroxy-4-[5-(4-{2- 1.58-1.60(m, 2H), 1.79-1.81 (m, 4H), DMSO-d₆ methyl-5-[2-(2- 2.31-2.33 (m, 6H),2.51-2.58 (m, 2H), morpholin-4-yl- 2.61 (s, 3H), 2.76 (m, 2H), 2.95 (m,2H), ethylamino)-ethyl]- 3.53 (m, 4H), 4.01-4.04 (m, 4H),thiazol-4-yl}-phenoxy)- 5.73 (s, 2H), 6.94-7.00 (m, 4H),pentyloxy]-benzamidine 7.51 (d, 2H), 7.60 (d, 2H) 218N-hydroxy-4-[5-(4-{5- 1.23 (m, 2H), 1.60 (m, 2H), 1.81 (m, 6H), DMSO-d₆[2-(3-imidazol-1-yl- 1.91 (m, 2H), 2.61 (s, 3H), 2.82 (m, 2H),propylamino)-ethyl]-2- 3.02 (m, 2H), 4.02 (m, 4H), methyl-thiazol-4-yl}-6.91-7.00 (m, 5H), 7.15 (s, 1H), 7.51 (d, 2H), phenoxy)-pentyloxy]- 7.59(d, 2H), 7.85 (d, 1H) benzamidine 219 N-hydroxy-4-(5-{4-[5- 1.05 (d,6H), 1.63 (m, 2H), CDCl₃ (2-isopropylamino- 1.81-1.85 (m, 4H), 2.65 (s,3H), ethyl)-2-methyl- 2.85-2.89 (m, 3H), 3.06-3.08 (m, 2H),thiazol-4-yl]-phenoxy}- 3.94-3.97 (m, 4H), 4.84 (brs, 2H),pentyloxy)-benzamidine 6.34 (brs, 1H), 6.85-6.89 (m, 4H), 7.46-7.51 (m,4H) 220 N-hydroxy-4-[5-(4-{5- 1.05 (d, 6H), 1.65 (m, 2H), CDCl₃[2-(3-isopropoxy- 1.79-1.84 (m, 6H), 2.64 (s, 3H), 2.77 (t, 2H),propylamino)-ethyl]-2- 2.91 (t, 2H), 3.15 (t, 2H), 3.40 (t, 2H),methyl-thiazole-4-yl}- 3.50 (m, 1H), 3.94-3.97 (m, 4H),phenoxy)-pentyloxy]- 4.93 (brs, 2H), 6.54 (brs, 1H), benzamidine6.84-6.88 (m, 4H), 7.45 (m, 4H) 221 N-hydroxy-4-(5-{4-[5- 0.85 (t, 3H),1.29-1.35 (m, 6H), DMSO-d₆ (2-butylamino-ethyl)-2- 1.58 (m, 2H), 1.78(m, 4H), 2.60 (s, 3H), methyl-thiazol-4-yl]- 2.72 (m, 2H), 2.93 (m, 2H),4.02 (m, 4H), phenoxy}-pentyloxy)- 5.72 (s, 2H), 6.91-6.97 (m, 4H),benzamidine 7.49-7.58 (m, 4H) 222 N-hydroxy-4-(5-{4-[5- 1.64 (m, 2H),1.86 (m, 4H), 2.66 (s, 3H), CDCl₃ (2-imidazol-1-yl- 3.30 (t, 2H),4.01-4.14 (m, 6H), ethyl)-2-methyl- 6.89-7.77 (m, 11H)thiazol-4-yl]-phenoxy}- pentyloxy)-benzamidine 223 N-hydroxy-4-(5-{4-[5-0.98-1.01 (m, 2H), 1.13-1.63 (m, 3H), DMSO-d₆ (2-cyclohexylamino-1.58-1.70 (m, 5H), 1.78-1.80 (m, 6H), ethyl)-2-methyl- 2.40 (m, 1H),2.60 (s, 3H), 2.79 (m, 2H), thiazol-4-yl]-phenoxy}- 2.95 (m, 2H),4.01-4.04 (m, 4H), pentyloxy)-benzamidine 5.72 (s, 2H), 6.93-7.00 (m,4H), 7.50 (d, 2H), 7.60 (d, 2H), 9.46 (s, 1H) 224 N-hydroxy-4-(5-{4-[5-0.93 (t, 6H), 1.59 (m, 2H), 1.79 (m, 4H), DMSO-d₆(2-diethylamino-ethyl)- 2.49 (m, 6H), 2.59 (s, 3H), 2.92 (m, 2H),2-methyl-thiazol-4-yl]- 4.02-4.04 (m, 4H), 5.72 (s, 2H),phenoxy}-pentyloxy)- 6.93-6.70 (m, 4H), 7.48-7.82 (m, 4H), benzamidine9.46 (s, 1H) 225 N-hydroxy-4-{5-[4-(5- 1.59 (m, 2H), 1.79 (m, 4H),DMSO-d₆ {2-[bis-(2-hydroxy- 2.55-2.59 (m, 4H), 2.60 (s, 3H), 2.75 (m,2H), ethyl)-amino]-ethyl}-2- 2.95 (m, 2H), 3.41-3.43 (m, 4H),methyl-thiazol-4-yl)- 4.01-.04 (m, 4H), 5.72 (s, 2H),phenoxy]-pentyloxy}- 6.93-7.00 (m, 4H), 7.50 (d, 2H), 7.59 (d, 2H),benzamidine 9.46 (s, 1H) 226 N-hydroxy-4-(5-{4-[5- 1.29-1.42 (m, 12H),1.65 (m, 2H), CDCl₃ (2-diisopropylamino- 1.84-1.89 (m, 4H), 2.71 (s,3H), 2.93 (m, 2H), ethyl)-2-methyl- 3.52 (m, 2H), 3.64 (m, 2H),thiazol-4-yl]-phenoxy}- 4.00-4.04 (m, 4H), 6.92 (m, 4H), 7.46 (d, 2H),pentyloxy)-benzamidine 7.78 (d, 2H) 227 N-hydroxy-4-[5-(4-{5- 1.03 (d,6H), 1.60-1.63 (m, 4H), DMSO-d₆ [2-(2,6-dimethyl- 1.78-1.80 (m, 4H),2.47-2.50 (m, 2H), morpholin-4-yl)-ethyl]- 2.60 (s, 3H), 2.74 (m, 2H),2.98 (m, 2H), 2-methyl-thiazol-4-yl}- 3.52-3.56 (m, 2H), 4.02-4.04 (m,4H), phenoxy)-pentyloxy]- 5.72 (s, 2H), 6.93-7.00 (m, 4H), benzamidine7.48 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) 228 N-hydroxy-4-(5-{4-[2- 1.58(m, 2H), 1.78-1.81 (m, 4H), DMSO-d₆ methyl-5-(2- 2.50-2.55 (m, 2H), 2.60(s, 3H), 2.62 (m, 4H), thiomorpholin-4-yl- 2.67 (m, 4H), 2.98 (m, 2H),ethyl)-thiazol-4-yl]- 4.02-4.04 (m, 4H), 5.72 (s, 2H),phenoxy}-pentyloxy)- 6.93-7.00 (m, 4H), 7.49 (d, 2H), 7.58 (d, 2H),benzamidine 9.46 (s, 1H) 229 N-hydroxy-4-(5-{4-[2- 1.59 (m, 2H), 1.79(m, 4H), 2.91 (m, 2H), DMSO-d₆ amino-5-(2-morpholin-4- 3.34 (m, 6H),3.63 (m, 4H), 4.03 (m, 4H), yl-ethyl)-thiazol-4- 5.76 (s, 2H), 6.93 (m,4H), 7.43 (d, 2H), yl]-phenoxy}- 7.59 (d, 2H), 9.53 (brs, 1H)pentyloxy)-benzamidine 230 N-hydroxy-4-[5-(4-{5- 1.57 (m, 2H), 1.78 (m,4H), 2.09 (s, 6H), DMSO-d₆ [2-(2-dimethylamino- 2.60 (s, 3H), 3.22-3.34(m, 8H), ethylamino)-ethyl]-2- 4.02 (m, 4H), 6.98 (d, 2H), 7.11 (d, 2H),methyl-thiazol-4-yl}- 7.50 (d, 2H), 7.76 (d, 2H) phenoxy)-pentyloxy]-benzamidine 231 N-hydroxy-4-(5-{4-[2- 1.63 (m, 2H), 1.83 (m, 4H), 2.49(m, 4H), CDCl₃ methyl-5-(2-morpholin- 2.59 (m, 2H), 2.65 (s, 3H), 3.03(m, 2H), 4-yl-ethyl)-thiazol-4- 3.71 (m, 4H), 3.98 (m, 4H), 4.95 (brs,1H), yl]-phenoxy}- 6.85-6.91 (d-d, 4H), 7.44-7.47 (d-d, 4H)pentyloxy)-benzamidine 232 N-hydroxy-4-[5-(4-{2- 1.64 (m, 2H), 1.83 (m,4H), 2.29 (s, 3H), CDCl₃ methyl-5-[2-(4-methyl- 2.58-2.63 (m, 10H), 2.64(s, 3H), piperazin-1-yl)-ethyl]- 2.99 (m, 2H), 3.96 (m, 4H), 4.85 (brs,1H), thiazol-4-yl}-phenoxy)- 6.85-6.89 (d-d, 4H), 7.43-7.71 (d-d, 4H)pentyloxy]-benzamidine 233 N-hydroxy-4-{5-[4-(5- 1.59 (m, 2H), 1.80 (m,4H), 2.60 (s, 3H), DMSO-d₆ {2-[bis-(2-methoxy- 2.66 (m, 4H), 2.73 (m,2H), 2.94 (m, 2H), ethyl)-amino]-ethyl}-2- 3.19 (s, 6H), 3.35 (m, 4H),4.03 (m, 4H), methyl-thiazol-4-yl)- 5.73 (s, 2H), 6.92 (d, 2H), 6.99 (d,2H), phenoxy]-pentyloxy}- 7.49 (d, 2H), 7.60 (d, 2H), 9.45 (s, 1H)benzamidine 234 N-hydroxy-4-(5-{4-[5- 1.06 (m, 9H), 1.58 (m, 2H), 1.80(m, 4H), DMSO-d₆ (2-tert-butylamino- 2.61 (s, 3H), 2.80 (m, 2H), 2.98(m, 2H), ethyl)-2-methyl- 4.03 (m, 4H), 6.91-7.01 (m, 4H),thiazol-4-yl]-phenoxy}- 7.50-7.82 (m, 4H) pentyloxy)-benzamidine 235N-hydroxy-4-(5-{4-[5- 0.86 (d, 6H), 1.59 (m, 2H), 1.80 (m, 5H), DMSO-d₆(2-isobutylamino- 2.60 (s, 3H), 2.73 (m, 2H), 2.94 (m, 2H),ethyl)-2-methyl- 3.34 (m, 2H), 4.02 (m, 4H), 5.72 (s, 2H),thiazol-4-yl]-phenoxy}- 6.93 (m, 4H), 7.49-7.60 (m, 4H),pentyloxy)-benzamidine 9.45 (s, 2H) 236 N-hydroxy-4-(5-{4-[5- 1.65 (m,2H), 1.88 (m, 4H), 2.10 (m, 2H), CDCl₃ (2-morpholin-4-yl- 2.92 (m, 4H),3.43 (m, 2H), 4.04 (m, 8H), ethyl)-2-pyridine-3-yl- 6.90-7.00 (m, 4H),7.37 (m, 1H), thiazol-4-yl]-phenoxy}- 7.57-7.60 (m, 4H), 8.24 (d, 1H),pentyloxy)-benzamidine 8.63 (d, 1H), 9.14 (s, 1H) 237N-hydroxy-4-[5-(4-{5- 1.70 (m, 2H), 1.89 (m, 4H), 2.81 (s, 3H), CDCl₃[2-(4-methyl-piperazin- 2.86 (m, 2H), 3.01-3.22 (m, 8H),1-yl)-ethyl]-2-pyridin- 3.46 (m, 2H), 4.05 (m, 4H), 3-yl-thiazol-4-yl}-6.95-6.97 (m, 4H), 7.53-7.59 (m, 4H), phenoxy)-pentyloxy]- 7.76 (m, 1H),8.35 (d, 1H), benzamidine 8.64 (d, 1H), 9.16 (s, 1H) 238N-hydroxy-4-(5-{4-[2- 1.60 (m, 2H), 1.82 (m, 4H), DMSO-d₆pyridin-3-yl-5-(2- 2.51-2.93 (m, 4H), 3.35-3.41 (m, 8H),thiomorpholin-4-yl- 4.08 (m, 4H), 6.97-7.08 (m, 4H),ethyl)-thiazol-4-yl]- 7.55 (m, 1H), 7.66-7.85 (m, 4H),phenoxy}-pentyloxy)- 8.31 (d, 1H), 8.68 (d, 1H), 9.13 (s, 1H)benzamidine 239 N-hydroxy-4-(5-{4-[5- 1.60 (m, 2H), 1.82 (m, 4H), 3.54(m, 2H), DMSO-d₆ (2-imidazol-1-yl- 4.07 (m, 4H), 4.53 (t, 2H),ethyl)-2-pyridin-3-yl- 6.99-7.17 (m, 5H), 7.53-7.75 (m, 6H),thiazol-4-yl]-phenoxy}- 7.85 (m, 1H), 8.30 (d, 1H), 8.71 (m, 1H),pentyloxy)-benzamidine 9.07 (s, 1H) 240 N-hydroxy-4-(5-{4-[2- 1.32 (d,6H), 1.58 (m, 2H), 1.78 (m, 4H), DMSO-d₆ isopropyl-5-(2- 2.39 (m, 4H),2.52 (m, 2H), 2.98 (m, 2H), morpholin-4-yl-ethyl)- 3.25 (m, 1H), 3.57(m, 4H), 4.04 (m, 4H), thiazol-4-yl]-phenoxy}- 5.72 (s, 2H), 6.96 (m,4H), 7.50 (d, 2H), pentyloxy)-benzamidine 7.59 (d, 2H), 9.46 (s, 1H) 241N-hydroxy-4-[5-(4-{2- 1.32 (d, 6H), 1.56 (m, 2H), 1.80 (m, 4H), DMSO-d₆isopropyl-5-[2-(4- 2.22 (s, 3H), 2.49 (m, 10H), 2.97 (m, 2H),methyl-piperazin-1-yl)- 3.22 (m, 1H), 4.04 (m, 4H), 5.72 (s, 2H),ethyl]-thiazol-4-yl}- 6.96 (m, 4H), 7.50 (d, 2H), 7.59 (d, 2H),phenoxy)-pentyloxy]- 9.46 (s, 1H) benzamidine 242 N-hydroxy-4-(5-{4-[5-1.31 (d, 6H), 1.59 (m, 2H), 1.79 (m, 4H), DMSO-d₆ (2-imidazol-1-yl- 3.27(m, 5H), 4.04 (m, 4H), 5.71 (s, 2H), ethyl)-2-isopropyl- 6.88 (s, 1H),6.98 (m, 4H), 7.14 (s, 1H), thiazol-4-yl]-phenoxy}- 7.40 (d, 2H), 7.58(d, 2H), 7.81 (d, 1H), pentyloxy)-benzamidine 9.45 (s, 1H) 243N-hydroxy-4-[5-(4-{2- 1.32 (d, 6H), 1.58 (m, 2H), 1.79 (m, 4H), DMSO-d₆isopropyl-5-[2-(2- 2.32 (m, 6H), 2.60 (m, 2H), 2.81 (m, 2H),morpholin-4-yl- 2.99 (m, 2H), 3.23 (m, 1H), 3.52 (m, 4H),ethylamino)-ethyl]- 4.03 (m, 4H), 5.71 (s, 2H), 6.98 (m, 4H),thiazol-4-yl}-phenoxy)- 7.53 (m, 4H) pentyloxy]-benzamidine 244N-hydroxy-4-[5-(4-{5- 1.32 (d, 6H), 1.57 (m, 2H), 1.81 (m, 6H), DMSO-d₆[2-(3-imidazol-1-yl- 2.43 (m, 2H), 2.74 (m, 2H), 2.94 (m, 2H),propylamino)-ethyl]-2- 3.22 (m, 1H), 4.01 (m, 6H), 5.71 (s, 2H),isopropyl-thiazol-4- 6.87 (s, 1H), 6.99 (m, 4H), 7.12 (s, 1H),yl}-phenoxy)- 7.57 (m, 4H), 7.82 (d, 1H) pentyloxy]-benzamidine 245N-hydroxy-4-(5-{4-[2- 1.32 (d, 6H), 1.58 (m, 2H), 1.80 (m, 4H), DMSO-d₆isopropyl-5-(2- 2.60 (m, 10H), 2.97 (m, 2H), 3.22 (m, 1H),thiomorpholin-4-yl- 4.01 (m, 4H), 5.70 (s, 2H), 6.92 (d, 2H),ethyl)-thiazol-4-yl]- 6.98 (d, 2H), 7.47 (d, 2H), 7.59 (d, 2H),phenoxy}-pentyloxy)- 9.44 (s, 1H) benzamidine 246 N-hydroxy-4-(5-{4-[2-1.21 (m, 2H), 1.42 (m, 4H), 1.59 (m, 2H), DMSO-d₆ cyclohexyl-5-(2- 1.62(m, 1H), 1.79 (m, 6H), 2.02 (m, 2H), morpholin-4-yl-ethyl)- 2.50 (m,4H), 2.90 (m, 1H), 2.98 (m, 2H), thiazol-4-yl]-phenoxy}- 3.56 (m, 4H),4.02 (m, 4H), 5.73 (s, 2H), pentyloxy)-benzamidine 6.93 (d, 2H), 6.99(d, 2H), 7.49 (d, 2H), 7.57 (d, 2H), 9.46 (s, 1H) 247N-hydroxy-4-[5-(4-{2- 1.22 (m, 1H), 1.42 (m, 4H), 1.58 (m, 2H), DMSO-d₆cyclohexyl-5-[2-(4- 1.68 (m, 1H), 1.79 (m, 6H), 2.04 (m, 2H),methyl-piperazin-1-yl)- 2.14 (m, 4H), 2.50 (m, 7H), 2.90 (m, 1H),ethyl]-thiazol-4-yl}- 2.97 (m, 2H), 3.45 (m, 2H), 4.01 (m, 4H),phenoxy)-pentyloxy]- 5.72 (m, 2H), 6.92 (d, 2H), 6.98 (d, 2H),benzamidine 7.48 (d, 2H), 7.57 (d, 2H), 9.46 (s, 1H) 248N-hydroxy-4-[5-(4-{2- 1.23 (m, 1H), 1.42 (m, 4H), 1.57 (m, 2H), DMSO-d₆cyclohexyl-5-[2-(2- 1.68 (m, 1H), 1.79 (m, 6H), 2.02 (m, 2H),morpholin-4-yl- 2.33 (m, 6H), 2.60 (m, 2H), 2.80 (m, 2H),ethylamino)-ethyl]- 2.91 (m, 1H), 2.98 (m, 2H), 3.52 (m, 4H),thiazol-4-yl}-phenoxy)- 4.02 (m, 4H), 5.72 (m, 2H), 6.90 (d, 2H),pentyloxy]-benzamidine 6.98 (d, 2H), 7.50 (d, 2H), 7.58 (d, 2H), 9.47(s, 1H) 249 N-hydroxy-4-(5-{4-[2- 1.25 (m, 1H), 1.42 (m, 4H), 1.58 (m,2H), DMSO-d₆ cyclohexyl-5-(2- 1.67 (m, 1H), 1.79 (m, 6H), 2.01 (m, 2H),thiomorpholin-4-yl- 2.56 (m, 2H), 2.60 (m, 4H), 2.67 (m, 4H),ethyl)-thiazol-4-yl]- 2.90 (m, 1H), 2.96 (m, 2H), 4.01 (m, 4H),phenoxy}-pentyloxy)- 5.72 (s, 2H), 6.91 (d, 2H), 6.99 (d, 2H),benzamidine 7.47 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) 250N-hydroxy-4-(5-{4-[2- 1.21 (m, 2H), 1.42 (m, 4H), 1.57 (m, 2H), DMSO-d₆cyclohexyl-5-(2- 1.67 (m, 1H), 1.78 (m, 6H), 2.02 (m, 2H),dimethylamino-ethyl)- 2.15 (s, 6H), 2.45 (t, 2H), 2.90 (m, 1H),thiazol-4-yl]-phenoxy}- 2.93 (t, 2H), 4.01 (m, 4H), 5.73 (s, 2H),pentyloxy)-benzamidine 6.93 (d, 2H), 6.98 (d, 2H), 7.49 (d, 2H), 7.58(d, 2H), 9.47 (s, 1H) 251 N-hydroxy-4-(5-{4-[2- 0.79 (m, 6H), 1.22 (m,1H), 1.32 (m, 4H), DMSO-d₆ cyclohexyl-5-(2- 1.35 (m, 4H0, 1.58 (m, 2H),1.66 (m, 1H), dipropylamino-ethyl)- 1.76 (m, 7H), 2.00 (m, 2H), 2.33 (m,3H), thiazol-4-yl]-phenoxy}- 2.60 (m, 2H), 2.92 (m, 3H), 4.01 (m, 4H),pentyloxy)-benzamidine 5.72 (s, 2H), 6.90 (d, 2H), 6.97 (d, 2H), 7.47(d, 2H), 7.57 (d, 2H), 9.46 (s, 1H) 252 N-hydroxy-4-(5-{4-[2- 0.20 (m,2H), 0.33 (m, 2H), 1.22 (m, 2H), DMSO-d₆ cyclohexyl-5-(2- 1.42 (m, 4H),1.58 (m, 2H), 1.65 (m, 1H), cyclopropylamino- 1.79 (m, 6H), 2.04 (m,3H), 2.80 (s, 2H), ethyl)-thiazol-4-yl]- 2.96 (m, 2H), 4.02 (m, 4H),5.72 (s, 2H), phenoxy}-pentyloxy)- 6.90 (d, 2H), 6.98 (d, 2H), 7.49 (d,2H), benzamidine 7.58 (d, 2H), 9.46 (s, 1H) 253 N-hydroxy-4-[5-(4-{2-1.58 (m, 1H), 1.79 (m, 4H), 2.35 (m, 6H), DMSO-d₆ amino-5-[2-(2- 2.69(m, 2H), 2.78 (m, 4H), 3.54 (m, 4H), morpholin-4-yl- 4.01 (m, 4H), 5.71(s, 2H), 6.93 (m, 4H), ethylamino)-ethyl]- 7.44 (d, 2H), 7.59 (d, 2H)thiazol-4-yl}-phenoxy)- pentyloxy]-benzamidine 254 N-hydroxy-4-(5-{4-[5-1.57 (m, 2H), 1.79 (m, 4H), 2.41 (m, 4H), DMSO-d₆ (2-morpholin-4-yl-2.55 (m, 2H), 3.06 (m, 2H), 3.59 (m, 4H), ethyl)-2-phenyl- 4.02 (m, 4H),7.01 (m, 4H), 7.57 (m, 7H), thiazol-4-yl]-phenoxy}- 7.92 (m, 2H)pentyloxy)-benzamidine 255 N-hydroxy-4-(5-{4-[2- 1.28 (t, 3H), 1.59 (m,2H), 1.79 (m, 4H), DMSO-d₆ ethyl-5-(2-morpholin-4- 2.39 (m, 4H), 2.49(m, 2H), 2.92 (q, 2H), yl-ethyl)-thiazol-4- 2.98 (t, 2H), 3.56 (t, 4H),4.01 (q, 4H), yl]-phenoxy}- 5.70 (s, 2H), 6.92 (d, 2H), 6.98 (d, 2H0,pentyloxy)-benzamidine 7.49 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) 256N-hydroxy-4-(5-{4-[2- 1.28 (m, 3H), 1.57 (m, 2H), 1.79 (m, 5H), DMSO-d₆ethyl-5-(2- 2.50 (m, 2H), 2.54 (d, 1H), 2.60 (m, 2H),thiomorpholin-4-yl- 2.66 (m, 2H), 2.91 (m, 4H), 3.16 (d, 2H),ethyl)-thiazol-4-yl]- 4.00 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H),phenoxy}-pentyloxy)- 6.98 (d, 2H0, 7.47 (d, 2H), 7.58 (d, 2H),benzamidine 9.43 (s, 1H) 257 N-hydroxy-4-(4-{4-[2- 1.89 (m, 4H), 2.39(m, 4H), 2.50 (m, 2H), DMSO-d₆ methyl-5-(2-morpholin- 2.60 (s, 3H), 2.98(t, 2H), 3.57 (t, 4H), 4-yl-ethyl)-thiazol-4- 4.06 (m, 4H), 5.71 (s,2H), 6.94 (d, 2H), yl]-phenoxy}-butoxy)- 6.99 (d, 2H), 7.49 (d, 2H0,7.58 (d, 2H), benzamidine 9.45 (s, 1H) 258 4-(5-{4-[2-cyclohexyl- 1.20(m, 2H), 1.41 (m, 4H), 1.59 (m, 2H), DMSO-d₆ 5-(2-morpholin-4-yl- 1.62(m, 1H), 1.78 (m, 6H), 2.01 (m, 2H), ethyl)-thiazol-4-yl]- 2.49 (m, 4H),2.90 (m, 1H), 2.98 (m, 2H), phenoxy}-pentyloxy)- 3.56 (m, 4H), 4.02 (m,4H), 6.93 (d, 2H), benzamidine 6.99 (d, 2H), 7.49 (d, 2H), 7.57 (d, 2H),9.10 (brs, 3H) 259 4-(5-{4-[2-methyl-5-(2- 1.59 (m, 2H), 1.81 (m, 4H),2.40 (m, 4H), DMSO-d₆ morpholin-4-yl-ethyl)- 2.60 (s, 3H), 2.96 (m, 2H),3.31 (m, 2H), thiazol-4-yl]-phenoxy}- 3.57 (m, 4H), 4.10 (m, 4H), 6.98(d, 2H), pentyloxy)-benzamidine 7.16 (d, 2H), 7.49 (d, 2H), 7.80 (d,2H), 9.09 (brs, 3H) 260 N-hydroxy-4-(5-{4-[2- 1.57 (m, 2H), 1.79 (m,4H), 2.39 (m, 4H), DMSO-d₆ methylamino-5-(2- 2.50 (m, 2H), 2.81 (s, 3H),2.84 (m, 2H), morpholin-4-yl-ethyl)- 3.58 (m, 4H), 4.00 (m, 4H), 5.74(brs, 2H), thiazol-4-yl]-phenoxy}- 6.92 (m, 4H), 7.27 (m, 1H), 7.44 (m,2H), pentyloxy)-benzamidine 7.59 (m, 2H), 9.47 (brs, 1H) 261N-hydroxy-4-[5-(4-{2- 1.58 (m, 2H), 1.80 (m, 4H), 2.50 (s, 3H), DMSO-d₆methylamino-5-[2-(4- 2.79 (m, 6H), 2.85 (s, 3H), 3.38 (m, 6H),methyl-piperazin-1-yl)- 4.01 (m, 4H), 5.75 (brs, 2H), 6.92 (m, 4H),ethyl]-thiazol-4-yl}- 7.43 (m, 2H), 7.60 (m, 2H), 9.46 (brs, 1H)phenoxy)-pentyloxy]- benzamidine 262 N-hydroxy-4-(5-{4-[2- 1.58 (m, 2H),1.79 (m, 4H), 2.60 (m, 4H), DMSO-d₆ methylamino-5-(2- 2.65 (m, 4H), 2.78(m, 4H), 3.33 (s, 3H), thiomorpholin-4-yl- 5.71 (s, 2H), 6.93 (m, 4H),7.43 (d, 2H), ethyl)-thiazol-4-yl]- 7.58 (d, 2H), 9.44 (s, 1H)phenoxy}-pentyloxy)- benzamidine 263 N-hydroxy-4-[5-(4-{2- 1.58 (m, 2H),1.79 (m, 4H), 2.30 (m, 4H), DMSO-d₆ methylamino-5-[2-(2- 2.55 (m, 4H),2.71 (m, 2H), 2.79 (m, 4H), morpholin-4-yl- 3.34 (s, 3H), 3.52 (m, 4H),4.00 (m, 4H), ethylamino)-ethyl]- 5.71 (s, 2H), 6.94 (m, 4H), 7.46 (d,2H0, thiazol-4-yl}-phenoxy)- 7.59 (d, 2H), 9.46 (s, 1H)pentyloxy]-benzamidine 264 N-hydroxy-4-[5-(4-{5- 1.58 (m, 2H), 1.78 (m,6H), 2.42 (m, 2H), DMSO-d₆ [2-(3-imidazol-1-yl- 2.66 (m, 2H), 2.78 (m,4H), 3.34 (s, 3H), propylamino)-ethyl]-2- 4.01 (m, 4H), 5.71 (s, 2H),6.86 (s, 1H), methylamino-thiazol-4- 6.94 (m, 4H), 7.13 (s, 1H), 7.25(d, 1H), yl}-phenoxy)- 7.44 (d.2H), 7.58 (d, 2H), 9.46 (s, 1H)pentyloxy]-benzamidine 265 4-(5-{4-[2-methylamino- 1.58 (m, 2H), 1.78(m, 4H), 2.40 (m, 4H), DMSO-d₆ 5-(2-morpholin-4-yl- 2.49 (m, 2H), 2.80(s, 3H), 2.84 (m, 2H), ethyl)-thiazol-4-yl]- 3.58 (m, 4H), 4.01 (m, 4H),6.92 (m, 4H), phenoxy}-pentyloxy)- 7.27 (m, 1H), 7.44 (m, 2H), 7.59 (m,2H), benzamidine 9.09 (brs, 3H) 266 N-hydroxy-4-(5-{4-[2- 1.58 (m, 2H),1.79 (m, 4H), 2.38 (m, 4H), DMSO-d₆ dimethylamino-5-(2- 2.48 (m, 2H),2.86 (t, 2H), 3.00 (s, 6H), morpholin-4-yl-ethyl)- 3.57 (m, 4H), 4.01(m, 4H), 5.71 (s, 2H), thiazol-4-yl]-phenoxy}- 6.94 (m, 4H), 7.45 (d,2H), 7.58 (d, 2H), pentyloxy)-benzamidine 9.45 (s, 1H) 267N-hydroxy-4-(5-{4-[2- 1.58 (m, 2H), 1.79 (m, 4H), 2.51 (m, 2H), DMSO-d₆dimethylamino-5-(2- 2.61 (m, 4H), 2.66 (m, 4H), 2.89 (m, 2H),thiomorpholin-4-yl- 3.00 (s, 6H), 4.01 (m, 4H), 5.71 (s, 2H),ethyl)-thiazol-4-yl]- 6.95 (m, 4H), 7.44 (d, 2H), 7.59 (d, 2H),phenoxy}-pentyloxy)- 9.44 (s, 1H) benzamidine 268 N-hydroxy-4-(5-{4-[2-1.15 (d, 6H), 1.58 (m, 2H), 1.79 (m, 4H), DMSO-d₆ (isobutyryl-methyl-2.40 (m, 4H), 2.78 (m, 1H), 2.97 (m, 2H), amino)-5-(2-morpholin- 3.33(s, 3H), 3.57 (m, 4H), 3.69 (m, 2H), 4-yl-ethyl)-thiazol-4- 4.01 (m,4H), 5.71 (s, 2H), 6.93 (d, 2H), yl]-phenoxy}- 6.99 (d, 2H), 7.51 (d,2H), 7.60 (d, 2H), pentyloxy)-benzamidine 9.44 (s, 1H) 269N-hydroxy-4-(5-{4-[2- 1.57 (m, 2H), 1.78 (m, 4H), 2.37 (m, 8H), DMSO-d₆[benzyl-(2-morpholin-4- 2.49 (m, 2H), 2.83 (m, 2H), 3.16 (m, 2H),yl-ethyl)-amino]-5-(2- 3.53 (m, 10H), 3.98 (m, 4H), 4.66 (s, 2H),morpholine-4-yl-ethyl)- 5.72 (s, 2H), 6.95 (m, 4H), 7.27 (m, 1H),thiazol-4-yl]-phenoxy}- 7.33 (m, 4H), 7.43 (m, 2H), 7.56 (m, 2H),pentyloxy)-benzamidine 9.46 (s, 1H) 270 N-hydroxy-4-(5-{4-[2- 1.15 (m,6H), 1.57 (m, 2H), 1.79 (m, 4H), DMSO-d₆ diethylamino-5-(2- 2.38 (m,4H), 2.48 (m, 2H), 2.83 (m, 2H), morpholin-4-yl-ethyl)- 3.40 (m, 4H),3.57 (m, 4H), 4.02 (m, 4H), thiazol-4-yl]-phenoxy}- 5.71 (s, 2H), 6.94(m, 4H), 7.45 (d, 2H), pentyloxy)-benzamidine 7.58 (d, 2H), 9.45 (s, 1H)271 N-hydroxy-4-(5-{4-[2- 1.57 (m, 2H), 1.79 (m, 4H), 2.39 (m, 4H),DMSO-d₆ [bis-(2-methoxy-ethyl)- 2.49 (m, 2H), 2.84 (m, 2H), 3.27 (s,6H), amino]-5-(2-morpholin- 3.56 (m, 12H), 4.01 (m, 4H), 5.71 (s, 2H),4-yl-ethyl)-thiazol-4- 6.93 (m, 4H), 7.43 (d, 2H), 7.59 (d, 2H),yl]-phenoxy}- 9.44 (s, 1H) pentyloxy)-benzamidine 272N-hydroxy-4-(5-{4-[2- 1.58 (m, 2H), 1.80 (m, 4H), 2.43 (m, 4H), DMSO-d₆morpholin-4-yl-5-(2- 3.32 (m, 8H), 3.58 (m, 8H), 4.05 (m, 4H),morpholin-4-yl-ethyl)- 5.71 (brs, 2H), 6.92 (m, 4H), 7.43 (m, 2H),thiazol-4-yl]-phenoxy}- 7.59 (m, 2H), 945 (brs, 1H)pentyloxy)-benzamidine 273 N-hydroxy-4-(5-{4-[2- 1.58 (m, 2H), 1.80 (m,4H), 2.68 (m, 8H), DMSO-d₆ morpholin-4-yl-5-(2- 2.85 (m, 2H), 3.33 (m,6H), 3.70 (m, 4H), thiomorpholin-4-yl- 4.02 (m, 4H), 5.71 (s, 2H), 6.95(m, 4H), ethyl)-thiazol-4-yl]- 7.44 (d, 2H), 7.59 (d, 2H), 9.44 (s, 1H)phenoxy}-pentyloxy)- benzamidine 274 N-hydroxy-4-[5-(4-{5- 1.58 (m, 2H),1.78 (m, 4H), 2.41 (s, 3H), DMSO-d₆ [2-(4-methyl-piperazin- 2.51 (m,5H), 2.75 (m, 3H), 2.88 (m, 2H), 1-yl)-ethyl]-2- 3.08 (m, 6H), 3.70 (m,4H), 4.01 (m, 4H), morpholin-4-yl-thiazol- 6.96 (m, 4H), 7.45 (d, 2H),7.69 (d, 2H) 4-yl}-phenoxy)- pentyloxy]-benzamidine 275N-hydroxy-4-[5-(4-{2- 1.59 (m, 2H), 1.79 (m, 4H), 2.30 (m, 4H), DMSO-d₆morpholin-4-yl-5-[2-(2- 2.50 (m, 4H), 2.97 (m, 2H), 3.37 (m, 4H),morpholin-4-yl- 3.50 (m, 6H), 3.71 (t, 4H), 4.01 (t, 4H),ethylamino)-ethyl]- 5.70 (d, 2H), 6.94 (m, 4H), 7.42 (d, 2H),thiazol-4-yl}-phenoxy)- 7.51 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H)pentyloxy]-benzamidine 276 N-hydroxy-4-(5-{4-[5- 1.38 (m, 2H), 1.49-1.56(m, 6H0, DMSO-d₆ (2-morpholin-4-yl- 1.76 (m, 4H), 2.37-2.49 (m, 8H),ethyl)-2-piperidin-1- 2.98 (m, 2H), 3.54 (m, 4H), 3.67 (m, 2H),yl-methyl-thiazol-4- 3.99 (m, 6H), 6.90-6.97 (m, 4H), yl]-phenoxy}-7.47-7.56 (m, 4H) pentyloxy)-benzamidine 277 4-(5-{4-[2-morpholin-4-1.59 (m, 2H), 1.80 (m, 4H), 2.43 (m, 4H), DMSO-d₆yl-5-(2-morpholin-4-yl- 3.32 (m, 8H), 3.598 (m, 8H), 4.05 (m, 4H),ethyl)-thiazol-4-yl]- 6.92 (m, 4H), 7.42 (m, 2H), 7.59 (m, 2H),phenoxy}-pentyloxy)- 9.10 (brs, 3H) benzamidine 278N-hydroxy-4-(5-{4-[5- 0.97 (d, 6H), 1.59 (m, 2H), 1.80 (m, 4H), DMSO-d₆(2-isobutyrylamino- 2.30 (m, 1H), 2.62 (s, 3H), 2.97 (m, 2H),ethyl)-2-methyl- 3.26 (m, 2H), 4.03 (m, 4H), 5.71 (s, 2H),thiazol-4-yl]-phenoxy}- 6.97 (m, 4H), 7.50 (d, 2H), 7.59 (d, 2H),pentyloxy)-benzamidine 7.96 (m, 1H), 9.45 (s, 1H) 279N-hydroxy-4-{5-[4-(5- 0.62 (d, 3H), 0.86 (d, 3H), 1.22 (s, 3H), DMSO-d₆{2-[isobutyl-(pyridin- 1.57 (m, 2H), 1.79 (m, 5H), 2.56 (s, 2H),3-carbonyl)-amino]- 2.66 (s, 1H), 2.98 (m, 2H), 3.15 (m, 1H),ethyl}-2-methyl- 3.21 (m, 1H), 3.42 (m, 1H), 3.63 (m, 1H),thiazol-4-yl)-phenoxy]- 4.02 (t, 2H), 4.09 (m, 2H), 5.72 (s, 2H),pentyloxy}-benzamidine 6.91 (d, 2H), 6.98 (d, 2H), 7.09 (d, 4H), 7.23(d, 2H), 8.59 (d, 2H), 9.45 (s, 1H) 280 N-hydroxy-4-{5-[4-(5- 0.37 (m,2H), 0.44 (m, 2H), 1.33 (d, 6H), DMSO-d₆ {2-[cyclopropyl- 1.58 (m, 2H),1.79 (m, 4H), 2.70 (m, 1H), (pyridin-4-carbonyl)- 3.24 (m, 2H), 3.35 (m,2H), 3.68 (m, 1H), amino]-ethyl}-2- 4.00 (m, 4H), 5.72 (s, 2H), 6.90 (d,2H), isopropyl-thiazol-4- 7.00 (m, 2H), 7.35 (m, 2H), 7.59 (m, 4H),yl)-phenoxy]- 8.63 (m, 2H), 9.45 (s, 1H) pentyloxy}-benzamidine 281N-hydroxy-4-{5-[4-(2- 0.36 (m, 2H), 0.47 (m, 2H), 1.22 (m, 1H), DMSO-d₆cyclohexyl-5-{2- 1.43 (m, 4H), 1.57 (m, 2H), 1.66 (m, 1H),[cyclopropyl-(pyridin- 1.78 (m, 6H), 2.02 (m, 2H), 2.77 (m, 1H),3-carbonyl)-amino]- 2.95 (m, 1H), 3.27 (m, 2H), 3.70 (m, 2H),ethyl}-thiazol-4-yl)- 4.02 (m, 4H), 5.72 (s, 2H), 6.90 (d, 2H),phenoxy]-pentyloxy}- 6.97 (m, 2H), 7.43 (m, 1H), 7.59 (m, 3H),benzamidine 7.82 (m, 2H), 8.60 (m, 2H), 9.46 (s, 1H) 282N-hydroxy-4-{5-[4-(5- 1.57 (m, 2H), 1.80 (m, 4H), 2.69 (s, 6H), DMSO-d₆methylcarbamoyl-2- 4.03 (m, 4H), 5.73 (brs, 2H), 6.97 (m,methyl-thiazol-4-yl)- 4H), 7.61 (m, 4H), 9.46 (brs, 1H)phenoxy]-pentyloxy}- benzamidine 283 N-hydroxy-4-{5-[4-(5- 1.04 (d, 6H),1.58 (m, 2H), 1.80 (m, 4H), DMSO-d₆ isopropylcarbamoyl-2- 2.70 (s, 3H),4.02 (m, 4H), 4.16 (m, 1H), methyl-thiazol-4-yl)- 5.73 (brs, 2H), 6.98(m, 4H), 7.60 (m, phenoxy]-pentyloxy}- 4H), 9.46 (brs, 1H) benzamidine284 N-hydroxy-4-{5-[4-(5- 1.57 (m, 2H), 1.77 (m, 6H), 2.11 (brs, DMSO-d₆{3-imidazol-1-yl- 3H), 3.36 (m, 2H), 3.91 (m, 2H), 4.00 (m,propylcarbamoyl}-2- 4H), 5.71 (m, 2H), 6.80 (m, 2H), 6.94 (m,methyl-thiazol-4-yl)- 4H), 7.25 (m, 2H), 7.56 (m, 1H), 7.75 (m,phenoxy]-pentyloxy}- 1H), 7.84 (m, 1H), 8.30 (brs, 1H) benzamidine 285N-hydroxy-4-{5-[4-(2- 1.57 (m, 2H), 1.78 (m, 4H), 2.60 (s, 3H), DMSO-d₆amino-5- 4.01 (m, 4H), 5.75 (brs, 2H), 6.914 (m, methylcarbamoyl- 4H),7.46 (m, 2H), 7.58 (m, 2H), thiazol-4-yl)-phenoxy]- 9.48 (brs, 1H)pentyloxy}-benzamidine 286 N-hydroxy-4-{5-[4-(2- 1.58 (m, 2H), 1.79 (m,4H), 2.59 (s, 3H), DMSO-d₆ methyl-5-morpholin-4- 2.78 (m, 4H), 3.73 (m,4H), 4.01 (m, 4H), yl-thiazol-4-yl)- 5.71 (s, 2H), 6.93-6.98 (m, 4H),phenoxy]-pentyloxy}- 7.58 (d, 2H), 8.05 (d, 2H), 9.45 (s, 1H)benzamidine 287 N-hydroxy-4-(5-{4-[2- 1.58 (m, 2H), 1.80 (m, 4H), 2.23(s, 3H), DMSO-d₆ methyl-5-(4-methyl- 2.48 (m, 4H), 2.58 (s, 3H), 2.80(m, 4H), piperazin-1-yl)- 4.02 (m, 4H), 5.71 (s, 2H), 6.96 (m, 4H),thiazol-4-yl]-phenoxy}- 7.59 (d, 1H), 7.83 (d, 1H), 8.04 (d, 2H),pentyloxy)-benzamidine 9.44 (s, 1H) 288 N-hydroxy-4-{5-[4-(2- 1.58 (m,2H), 1.81 (m, 4H), 2.72 (m, 4H), DMSO-d₆ amino-5-morpholin-4-yl- 3.17(s, 2H), 3.71 (m, 4H), 4.03 (m, 4H), thiazol-4-yl)-phenoxy]- 6.80 (d,1H), 6.91 (d, 1H), 6.99 (d, 2H), pentyloxy}-benzamidine 7.62 (d, 2H),7.83 (d, 1H), 8.01 (d, 1H) 289 N-hydroxy-4-(5-{4-[5- 1.58 (m, 2H), 1.79(m, 4H), 2.23 (s, 3H), DMSO-d₆ (4-methyl-piperazin-1- 2.49 (m, 4H), 2.77(m, 4H), 3.36 (m, 4H), yl)-2-morpholin-4-yl- 3.70 (m, 4H), 4.02 (m, 4H),5.72 (s, 2H), thiazol-4-yl]-phenoxy}- 6.94 (m, 4H), 7.59 (d, 2H), 8.05(d, 2H), pentyloxy)-benzamidine 9.45 (s, 1H) 290 N-hydroxy-4-{5-[4-(2,5-1.60 (m, 2H), 1.79 (m, 4H), 2.75 (m, 4H), DMSO-d₆ di-morpholin-4-yl-3.39 (m, 4H), 3.72 (m, 8H), 4.01 (m, 4H), thiazol-4-yl)-phenoxy]- 5.72(s, 2H), 6.93 (m, 4H), 7.59 (d, 2H), pentyloxy}-benzamidine 8.06 (d,2H), 9.45 (s, 1H) 291 N-hydroxy-4-{5-[4-(2- 1.60 (m, 2H), 1.79 (m, 4H),2.51 (m, 6H), DMSO-d₆ morpholin-4-yl-5- 2.77 (m, 2H), 2.98 (m, 2H), 3.34(m, 4H), thiomorpholin-4-yl- 3.70 (m, 6H), 4.02 (m, 4H), 5.72 (s, 2H),thiazol-4-yl)-phenoxy]- 6.92 (m, 4H), 7.59 (d, 2H), 7.77 (d, 1H),pentyloxy}-benzamidine 8.03 (d, 1H), 9.45 (s, 1H) 292N-hydroxy-4-{5-[4-(2- 1.59 (m, 2H), 1.80 (m, 4H), 1.89 (m, 4H), DMSO-d₆morpholin-4-yl-5- 2.91 (m, 4H), 3.36 (m, 4H), 3.70 (m, 4H),pyrolidin-1-yl-thiazol- 4.02 (m, 4H), 5.72 (s, 2H), 6.93 (m, 4H),4-yl)-phenoxy]- 7.48 (d, 2H), 7.94 (d, 2H), 9.45 (s, 1H)pentyloxy}-benzamidine 293 N-hydroxy-4-{5-[4-(2- 1.59 (m, 2H), 1.80 (m,4H), 2.51 (m, 4H), DMSO-d₆ methyl-5-morpholin-4- 3.34 (s, 3H), 3.61 (m,4H), 3.77 (s, 2H), ylmethyl-thiazol-4-yl)- 4.03 (m, 4H), 5.71 (s, 2H),6.92 (d, 2H), phenoxy]-pentyloxy}- 7.01 (d, 2H), 7.58 (m, 4H), 9.44 (s,1H) benzamidine 294 N-hydroxy-4-(5-{4-[2- 1.61 (m, 2H), 1.81 (m, 4H),2.17 (s, 3H), DMSO-d₆ methyl-5-(4-methyl- 2.35 (m, 4H), 2.51 (m, 4H),3.33 (s, 3H), piperazin-1-ylmethyl)- 3.75 (s, 1H), 3.80 (s, 1H), 4.03(m, 4H), thiazol-4-yl]-phenoxy}- 5.71 (s, 2H), 6.92 (d, 2H), 7.01 (d,2H), pentyloxy)-benzamidine 7.58 (m, 4H), 9.44 (s, 1H) 295N-hydroxy-4-{5-[4-(2- 1.59 (m, 2H), 1.80 (m, 4H), 2.65 (m, 4H), DMSO-d₆methyl-5-thiomorpholin- 2.78 (m, 4H), 3.33 (s, 3H), 3.79 (s, 2H),4-ylmethyl-thiazol-4- 4.03 (m, 4H), 5.71 (s, 2H), 6.93 (d, 2H),yl)-phenoxy]- 7.00 (d, 2H), 7.58 (m, 4H), 9.44 (s, 1H)pentyloxy}-benzamidine 296 N-hydroxy-4-{5-[4-(2- 1.41 (m, 2H), 1.53 (m,4H), 1.59 (m, 2H), DMSO-d₆ methyl-5-piperidin-1- 1.80 (m, 4H), 2.49 (m,4H), 3.33 (s, 3H), ylmethyl-thiazol-4-yl)- 3.70 (s, 1H), 3.75 (s, 1H),4.03 (m, 4H), phenoxy]-pentyloxy}- 5.71 (s, 2H), 6.92 (d, 2H), 7.01 (d,2H), benzamidine 7.58 (m, 4H), 9.44 (s, 1H) 297 N-hydroxy-4-{5-[4-(5-1.59 (m, 2H), 1.80 (m, 4H), 2.28 (d, 6H), DMSO-d₆ dimethylaminomethyl-2-3.33 (s, 3H), 3.69 (s, 1H), 3.74 (s, 1H), methyl-thiazol-4-yl)- 4.03 (m,4H), 5.71 (s, 2H), 6.92 (d, 2H), phenoxy]-pentyloxy}- 7.01 (d, 2H), 7.58(m, 4H), 9.44 (s, 1H) benzamidine 298 N-hydroxy-4-{5-[4-(5- 0.88 (t,3H), 1.32-1.42 (m, 4H), DMSO-d₆ butylaminomethyl-2- 1.58 (m, 2H), 1.80(m, 4H), 2.48 (s, 3H), methyl-thiazol-4-yl)- 2.51 (m, 2H), 3.92 (s, 2H),4.02 (m, 4H), phenoxy]-pentyloxy}- 5.72 (s, 2H), 6.91-6.98 (m, 4H),benzamidine 7.55-7.61 (m, 4H), 9.46 (s, 1H) 299 N-hydroxy-4-(5-{4-[5-0.89 (d, 6H), 1.58 (m, 2H), 1.68 (m, 1H), DMSO-d₆(isobutylamino-methyl)- 1.80 (m, 4H), 2.40 (d, 2H), 2.48 (s, 3H),2-methyl-thiazol-4-yl]- 3.91 (s, 2H), 4.02 (m, 4H), 5.72 (s, 2H),phenoxy}-pentyloxy)- 6.92 (d, 2H), 7.00 (d, 2H), benzamidine 7.55-7.60(m, 4H), 9.45 (s, 1H) 300 N-hydroxy-4-(5-{4-[5- 1.08 (s, 9H), 1.58 (m,2H), 1.81 (m, 4H), DMSO-d₆ (tert-butylamino- 2.47 (s, 3H), 3.88 (s, 2H),4.02 (m, 4H), methyl)-2-methyl- 5.72 (s, 2H), 6.93 (d, 2H), 6.98 (d,2H), thiazol-4-yl]-phenoxy}- 7.55-7.58 (m, 4H), 9.46 (s, 1H)pentyloxy)-benzamidine 301 N-hydroxy-4-{5-[4-(2- 0.86 (t, 3H), 1.44-1.46(m, 2H), DMSO-d₆ methyl-5- 1.58 (m, 2H), 1.80 (m, 4H), 2.48 (s, 3H),propylaminomethyl- 2.51 (m, 2H), 3.91 (s, 2H), 4.02 (m, 4H),thiazol-4-yl)-phenoxy]- 5.72 (s, 2H), 6.92 (d, 2H), 6.97 (d, 2H),pentyloxy}-benzamidine 7.55-7.60 (m, 4H), 9.46 (s, 1H) 302N-hydroxy-4-[5-(4-{2- 1.58 (m, 2H), 1.80 (m, 4H), 2.35 (m, 2H), DMSO-d₆methyl-5-[(2-morpholin- 2.40 (m, 4H), 2.48 (s, 3H), 2.70 (m, 2H),4-yl-ethylamino)- 3.56 (m, 4H), 3.95 (s, 2H), 4.01 (m, 4H),methyl]-thiazol-4-yl}- 5.72 (s, 2H), 6.93 (d, 2H), 6.99 (d, 2H),phenoxy)-pentyloxy]- 7.55-7.60 (m, 4H), 9.46 (s, 1H) benzamidine 303N-hydroxy-4-[5-(4-{5- 1.59 (m, 2H), 1.78 (m, 4H), 1.85 (m, 2H), DMSO-d₆[(3-imidazol-1-yl- 2.48 (s, 3H), 2.51 (m, 4H), 3.91 (s, 2H),propylamino)-methyl]-2- 4.02 (m, 4H), 5.72 (s, 2H), 6.87 (s, 1H),methyl-thiazol-4-yl}- 6.93 (d, 2H), 6.98 (m, 3H), 7.16 (s, 1H),phenoxy)-pentyloxy]- 7.55-7.61 (m, 4H), 9.46 (s, 1H) benzamidine 304N-hydroxy-4-{5-[4-(2- 1.59 (m, 2H), 1.69 (m, 4H), 1.80 (m, 4H), DMSO-d₆methyl-5-pyrolidin-1- 2.49 (m, 4H), 2.62 (s, 1.603H),ylmethyl-thiazol-4-yl)- 3.79 (s, 2H), 4.03 (m, 4H), 5.73 (s, 2H),phenoxy]-pentyloxy}- 6.93-7.00 (m, 4H), 7.54-7.58 (m, 4H), benzamidine9.46 (s, 1H) 305 N-hydroxy-4-{5-[4-(5- 1.58 (m, 2H), 1.79 (m, 4H), 2.48(s.3H), DMSO-d₆ imidazol-1-ylmethyl-2- 4.03 (m, 4H), 5.54 (s, 2H), 5.72(s, 2H), methyl-thiazol-4-yl)- 6.94 (m, 3H), 7.02 (d, 2H), 7.29 (s, 1H),phenoxy]-pentyloxy}- 7.56-7.61 (m, 4H), 7.81 (s, 1H), benzamidine 9.46(s, 1H) 306 N-hydroxy-4-(5-{4-[5- 1.58 (m, 2H), 1.79 (m, 4H), 2.49(s.3H), DMSO-d₆ (benzylamino-methyl)-2- 3.78 (s, 2H), 3.91 (s, 2H), 4.01(m, 4H), methyl-thiazol-4-yl]- 5.72 (s, 2H) 6.92 (d, 2H), 7.00 (d, 2H),phenoxy}-pentyloxy)- 7.25 (m, 1H), 7.36 (m, 4H) benzamidine 7.55-7.61(m, 4H), 9.46 (s, 1H) 307 N-hydroxy-4-{5-[4-(5- 0.30 (m, 2H), 0.39 (m,2H), 1.59 (m, 2H), DMSO-d₆ cyclopropylaminomethyl- 1.80 (m, 4H), 2.20(m, 1H), 2.48 (s, 3H), 2-methyl-thiazol-4-yl)- 3.96 (s, 2H), 4.02 (m,4H), 5.72 (s, 2H), phenoxy]-pentyloxy}- 6.92 (d, 2H), 7.00 (d, 2H), 7.58(m, 4H), benzamidine 9.45 (s, 1H) 308 N-hydroxy-4-{5-[4-(2- 1.58 (m,2H), 1.80 (m, 4H), 2.72 (m, 4H), DMSO-d₆ methylamino-5- 3.34 (s, 3H),3.71 (m, 4H), 4.01 (m, 4H), morpholin-4-yl-thiazol- 5.77 (s, 2H), 6.92(m, 4H), 7.59 (d, 2H), 4-yl)-phenoxy]- 8.05 (d, 2H), 9.47 (s, 1H)pentyloxy}-benzamidine 309 N-hydroxy-4-(5-{4-[2- 1.59 (m, 2H), 1.78 (m,4H), 2.40 (m, 4H), DMSO-d₆ (methyl-pyridin-4- 3.07 (s, 3H), 3.34 (m,2H), 3.56 (m, 4H), ylmethyl-amino)-5- 4.01 (m, 4H), 4.73-4.80 (m, 2H),morpholin-4-ylmethyl- 5.72 (brs, 2H), 6.91 (m, 4H), 7.28 (m, 2H),thiazol-4-yl]-phenoxy}- 7.49 (m, 2H), 7.57 (m, 2H), 8.53 (m, 2H),pentyloxy)-benzamidine 9.45 (brs, 1H) 310 N-hydroxy-4-[5-(4-{2- 1.58 (m,2H), 1.78 (m, 4H), 2.40 (m, 4H), DMSO-d₆ [(2-hydroxy-ethyl)- 3.04 (s,3H), 3.37 (m, 4H), 3.46 (m, 2H), methyl-amino]-5- 3.60 (m, 4H), 3.98 (m,4H), 4.82 (t, 1H), morpholin-4-ylmethyl- 5.72 (brs, 2H), 6.88 (m, 4H),7.42 (d, 2H), thiazol-4-yl}-phenoxy)- 7.58 (d, 2H), 9.45 (brs, 1H)pentyloxy]-benzamidine 311 N-hydroxy-4-(5-{4-[2- 1.12 (t, 3H), 1.58 (m,2H), 1.79 (m, 4H), DMSO-d₆ (ethyl-methyl-amino)-5- 2.50 (m, 4H), 2.97(s, 3H), 3.01 (m, 2H), morpholin-4-ylmethyl- 3.35 (m, 2H), 3.44 (m, 4H),3.98 (m, 4H), thiazol-4-yl]-phenoxy}- 5.72 (brs, 2H), 6.89 (m, 4H), 7.42(d, 2H), pentyloxy)-benzamidine 7.58 (d, 2H), 9.46 (brs, 1H) 312N-hydroxy-4-(5-{4-[2- 1.57-1.60 (m, 2H), 1.77-1.81 (m, 4H), DMSO-d₆(benzyl-methyl-amino)- 2.40 (s, 4H), 3.00 (s, 3H), 3.55 (s, 6H),5-morpholin-4-ylmethyl- 4.01-4.03 (m, 4H), 4.68 (s, 2H),thiazol-4-yl]-phenoxy}- 5.71 (s, 2H), 6.92 (d, 2H), 6.98 (d, 2H),pentyloxy)-benzamidine 7.28-7.37 (m, 5H), 7.52 (d, 2H), 7.59 (d, 2H),9.45 (s, 1H) 313 N-hydroxy-4-[5-(4-{2- 1.58 (m, 2H), 1.79 (m, 4H), 2.40(m, 8H), DMSO-d₆ [methyl-(2-morpholin-4- 2.51 (m, 4H), 3.01 (s, 3H),3.55 (m, 12H), yl-ethyl)-amino]-5- 3.99 (m, 4H), 5.74 (m, 2H), 6.91 (d,2H), morpholin-4-ylmethyl- 6.93 (d, 2H), 7.49 (d, 2H), 7.60 (d, 2H),thiazol-4-yl}-phenoxy)- 9.48 (s, 1H) pentyloxy]-benzamidine 314N-hydroxy-4-[5-(4-{2- 1.59 (m, 2H), 1.77 (m, 4H), 2.41 (m, 4H), DMSO-d₆[methyl-(2-morpholin-4- 2.51 (m, 2H), 2.63 (m, 8H), 3.01 (s, 3H),yl-ethyl)-amino]-5- 3.54 (m, 8H), 4.00 (m, 4H), 5.74 (m, 2H),thiomorpholin-4- 6.93 (m, 4H), 7.47 (d, 2H), 7.61 (d, 2H),ylmethyl-thiazol-4-yl}- 9.49 (s, 1H) phenoxy)-pentyloxy]- benzamidine315 N-hydroxy-4-[5-(4-{5- 1.58 (m, 2H), 1.80 (m, 4H), 2.43 (m, 4H),DMSO-d₆ {[bis-(2-methoxy- 2.50 (m, 2H), 2.63 (m, 2H), 3.01 (s, 3H),ethyl)-amino]-methyl}- 3.18 (m, 4H), 3.36 (m, 8H), 3.55 (m, 6H),2-[methyl-(2-morpholin- 3.74 (m, 2H), 4.01 (m, 4H), 5.72 (s, 2H),4-yl-ethyl)-amino]- 6.92 (m, 4H) 7.42 (d, 2H), 7.59 (d, 2H),thiazol-4-yl}-phenoxy)- 9.46 (s, 1H) pentyloxy]-benzamidine 316N-hydroxy-4-(5-{4-[2- 1.58 (m, 2H), 1.80 (m, 4H), 2.16 (s, 3H), DMSO-d₆[methyl-(2-morpholin-4- 2.42 (m, 6H), 3.01 (s, 3H), 3.17 (m, 8H),yl-ethyl)-amino]-5-(4- 3.55 (m, 8H), 4.01 (m, 4H), 5.71 (m, 2H),methyl-piperazin-1- 6.94 (m, 4H), 7.48 (d, 2H), 7.59 (d, 2H),ylmethyl)-thiazol-4- 9.46 (s, 1H) yl]-phenoxy}- pentyloxy)-benzamidine317 N-hydroxy-4-[5-(4-{5- 0.98 (d, 6H), 1.58 (m, 2H), 1.80 (m, 4H),DMSO-d₆ (isopropylamino- 2.42 (m, 4H), 2.51 (m, 1H), 3.02 (s, 3H),methyl)-2-[methyl-(2- 3.31 (m, 2H), 3.54 (m, 6H), 3.79 (m, 2H),morpholin-4-yl-ethyl)- 4.00 (m, 4H), 5.72 (s, 2H), amino]-thiazol-4-yl}-6.93-6.96 (m, 4H), 7.49 (d, 2H), 7.58 (d, 2H), phenoxy)-pentyloxy]- 8.32(s, 1H), 9.45 (s, 1H) benzamidine 318 N-hydroxy-4-[5-(4-{5- 1.57 (m,2H), 1.78 (m, 4H), 2.42 (m, 4H), DMSO-d₆ [(2-methoxy- 2.50 (m, 6H), 3.02(s, 3H), 3.36 (m, 5H), ethylamino)-methyl]-2- 3.53 (m, 6H), 4.00 (m,4H), 5.71 (brs, 2H), [methyl-(2-morpholin-4- 6.91 (m, 4H), 7.44 (m, 2H),7.59 (m, 2H), yl-ethyl)-amino]- 9.46 (brs, 1H) thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine 319 N-hydroxy-4-[5-(4-{2- 1.58 (m, 2H), 1.80 (m,4H), 2.37 (m, 4H), DMSO-d₆ [(2-methoxy-ethyl)- 3.03 (s, 3H), 3.26 (s,3H), 3.55 (m, 10H), methyl-amino]-5- 4.00 (m, 4H), 5.72 (s, 2H),morpholin-4-ylmethyl- 6.93-6.97 (m, 4H), 7.49 (d, 2H), 7.59 (d, 2H),thiazol-4-yl}-phenoxy)- 9.46 (s, 1H) pentyloxy]-benzamidine 320N-hydroxy-4-(5-{4-[2- 0.88 (t, 3H), 1.59 (m, 4H), 1.79 (m, 4H), DMSO-d₆(methyl-propyl-amino)- 2.39 (m, 4H), 3.00 (s, 3H), 3.35 (m, 2H),5-morpholin-4-ylmethyl- 3.55 (m, 6H), 4.00 (m, 4H), 5.72 (s, 2H),thiazol-4-yl]-phenoxy}- 6.95 (m, 4H), 7.49 (d, 2H), 7.60 (d, 2H),pentyloxy)-benzamidine 9.45 (s, 1H) 321 N-hydroxy-4-(5-{4-[2- 1.58 (m,2H), 1.78 (m, 4H), 2.38 (m, 4H), DMSO-d₆ (methyl-pyridin-3- 3.03 (s,3H), 3.56 (m, 6H), 4.01 (m, 4H), ylmethyl-amino)-5- 4.72 (s, 2H), 5.72(s, 2H), 6.92 (d, 2H), morpholin-4-ylmethyl- 6.98 (d, 2H), 7.39 (m, 1H),7.52 (d, 2H), thiazol-4-yl]-phenoxy}- 7.59 (d, 2H), 7.74 (m, 1H), 8.49(m, 1H), pentyloxy)-benzamidine 8.57 (m, 1H), 9.46 (s, 1H) 322N-hydroxy-4-{5-[4-(2- 1.58 (m, 2H), 1.79 (m, 4H), 2.50 (s, 3H), DMSO-d₆methyl-5-methylamino- 2.61 (s, 3H), 4.04 (m, 4H), 5.70 (s, 2H),thiazol-4-yl)-phenoxy]- 6.92 (m, 4H), 7.58 (d, 2H), 7.89 (d, 1H),pentyloxy}-benzamidine 7.97 (d, 1H), 9.43 (s, 1H) 323N-hydroxy-4-[5-(4-{2- 1.20 (m, 2H), 1.84 (m, 4H), 2.65 (s, 3H), DMSO-d₆methyl-5-[(pyridin-4- 4.01 (m, 4H), 5.73 (s, 2H), 6.92 (d, 2H),carbonyl)-amino]- 7.01 (d, 2H), 7.58 (d, 2H), 7.74 (d, 2H),thiazol-4-yl}-phenoxy)- 7.85 (d, 2H), 8.80 (d, 2H), 9.45 (s, 1H)pentyloxy]-benzamidine 324 N-hydroxy-4-[5-(4-{2- 1.58 (m, 2H), 1.78 (m,4H), 2.64 (s, 3H), DMSO-d₆ methyl-5-[(pyridin-3- 4.01 (m, 4H), 5.70 (s,2H), 6.91 (d, 2H), carbonyl)-amino]- 7.02 (d, 2H), 7.58 (m, 3H), 7.78(d, 2H), thiazol-4-yl}-phenoxy)- 8.29 (d, 1H), 8.77 (d, 1H), 9.10 (s,1H), pentyloxy]-benzamidine 9.43 (s, 1H) 325 N-hydroxy-4-[5-(4-{2- 1.58(m, 2H), 1.79 (m, 4H), 4.07 (m, 4H), DMSO-d₆ phenyl-5-[(pyridin-3- 7.06(d, 1H), 7.09 (m, 3H), 7.51 (m, 5H), carbonyl)-amino]- 7.87 (m, 3H),7.97 (d, 2H), 8.32 (d, 1H), thiazol-4-yl}-phenoxy)- 8.79 (d, 1H), 9.13(s, 1H) pentyloxy]-benzamidine 326 N-hydroxy-4-{5-[4-(5- 1.58 (m, 2H),1.79 (m, 4H), 2.57 (s, 3H), DMSO-d₆ dimethylamino-2-methyl- 2.61 (s,6H), 4.00 (m, 4H), 5.70 (s, 2H), thiazol-4-yl)-phenoxy]- 6.91 (d, 2H),6.96 (d, 2H), 7.59 (d, 2H), pentyloxy}-benzamidine 7.98 (d, 2H), 9.44(s, 1H) 327 N-hydroxy-4-{5-[4-(5- 1.58 (m, 2H), 1.79 (m, 4H), 2.70 (s,6H), DMSO-d₆ dimethylamino-2-phenyl- 4.02 (m, 4H), 5.71 (s, 2H), 6.92(d, 2H), thiazol-4-yl)-phenoxy]- 7.01 (d, 2H), 7.47 (m, 3H), 7.60 (d,2H), pentyloxy}-benzamidine 7.89 (d, 2H), 8.04 (d, 2H), 9.46 (s, 1H) 328N-hydroxy-4-{5-[4-(2- 1.23 (m, 1H), 1.41 (m, 4H), 1.59 (m, 2H), DMSO-d₆cyclohexyl-5- 1.65 (m, 1H), 1.79 (m, 6H), 2.03 (m, 2H),dimethylamino-thiazol- 2.61 (s, 6H), 2.85 (m, 1H), 4.01 (m, 4H),4-yl)-phenoxy]- 5.72 (s, 2H), 6.94 (m, 4H), 7.60 (d, 2H),pentyloxy}-benzamidine 7.99 (d, 2H), 9.46 (s, 1H). 329N-hydroxy-4-{5-[4-(2- 1.55 (m, 2H), 1.76 (m, 4H), 2.74 (s, 3H), DMSO-d₆methyl-5- 3.99 (m, 4H), 5.71 (s, 2H), 6.90 (m, 4H), [1,2,4]triazol-1-yl-7.17 (d, 2H), 7.58 (d, 2H), 8.36 (s, 1H), thiazol-4-yl)-phenoxy]- 8.84(s, 1H), 9.45 (s, 1H) pentyloxy}-benzamidine 330 N-hydroxy-4-{5-[4-(5-1.59 (m, 2H), 1.80 (m, 4H), 4.02 (m, 4H), DMSO-d₆amino-2-phenyl-thiazol- 5.73 (s, 2H), 5.88 (s, 2H), 6.94 (d, 2H),4-yl)-phenoxy]- 6.98 (d, 2H), 7.40 (t, 1H), 7.42 (d, 2H),pentyloxy}-benzamidine 7.59 (d, 2H), 7.74 (d, 2H), 7.76 (d, 2H), 9.45(s, 1H) 331 N-hydroxy-4-{5-[4-(5- 1.58 (m, 2H), 1.77 (m, 4H), 2.44 (s,3H), DMSO-d₆ amino-2-methyl-thiazol- 3.99 (m, 4H), 5.34 (s, 2H), 5.71(s, 2H), 4-yl)-phenoxy]- 6.92 (m, 4H), 7.59 (d, 2H), 7.67 (d, 2H),pentyloxy}-benzamidine 9.44 (s, 1H) 332 N-hydroxy-4-{5-[4-(5- 1.60 (m,2H), 1.81 (m, 4H), 4.03 (m, 4H), DMSO-d₆ amino-2-pyridin-3-yl- 5.72 (s,2H), 6.05 (s, 2H), 6.92 (d, 2H), thiazol-4-yl)-phenoxy]- 7.00 (d, 2H),7.45 (d, 1H), 7.59 (d, 2H), pentyloxy}-benzamidine 7.75 (d, 2H), 8.10(d, 1H), 8.52 (t, 1H), 8.95 (s, 1H), 9.45 (s, 1H) 333N-hydroxy-4-{5-[4-(5- 1.23 (t, 3H), 1.58 (m, 2H), 1.78 (m, 4H), DMSO-d₆amino-2-ethyl-thiazol- 2.78 (q, 2H), 4.01 (m, 4H), 5.38 (s, 2H),4-yl)-phenoxy]- 5.72 (s, 2H), 6.93 (d, 4H), 7.59 (d, 2H),pentyloxy}-benzamidine 7.67 (d, 2H), 9.46 (s, 1H). 334N-hydroxy-4-{5-[4-(5- 1.23 (m, 1H), 1.36 (m, 4H), 1.57 (m, 2H), DMSO-d₆amino-2-cyclohexyl- 1.64 (m, 1H), 1.81 (m, 6H), 1.98 (m, 2H),thiazol-4-yl)-phenoxy]- 2.74 (m, 1H), 4.00 (m, 4H), 5.36 (s, 2H),pentyloxy}-benzamidine 5.71 (s, 2H), 6.92 (d, 4H), 7.59 (d, 2H), 7.66(d, 2H), 9.45 (s, 1H). 335 N-hydroxy-4-{5-[4-(2- 1.58 (m, 2H), 1.78 (m,4H), 2.41 (m, 4H), DMSO-d₆ methylamino-5- 2.80 (s, 3H), 3.34 (m, 2H),3.56 (m, 4H), morpholin-4-ylmethyl- 4.01 (m, 4H), 5.73 (brs, 2H), 6.92(m, 4H), thiazol-4-yl)-phenoxy]- 7.36 (m, 1H), 7.49 (d, 2H), 7.59 (d,2H), pentyloxy}-benzamidine 9.46 (brs, 1H) 336 N-hydroxy-4-{5-[4-(2-1.60 (m, 2H), 1.80 (m, 4H), 2.38 (m, 4H), DMSO-d₆ morpholin-4-yl-5- 3.35(m, 4H), 3.57 (m, 6H), 3.70 (m, 4H), morpholin-4-ylmethyl- 4.03 (m, 4H),5.72 (s, 2H), 7.49 (d, 2H), thiazol-4-yl)-phenoxy]- 7.59 (d, 2H), 9.45(s, 1H) pentyloxy}-benzamidine 337 N-hydroxy-4-{5-[4-(5- 1.59 (m, 8H),1.79 (m, 4H), 2.75 (m, 4H), DMSO-d₆ morpholin-4-yl-2- 3.41 (m, 4H), 3.73(m, 4H), 4.00 (m, 4H), piperidin-1-yl-thiazol- 5.72 (s, 2H), 6.92 (m,4H), 7.59 (d, 2H), 4-yl)-phenoxy]- 8.06 (d, 2H), 9.45 (s, 1H)pentyloxy}-benzamidine

EXAMPLE 1 Effect of Individual or Combination Treatment of EtidronicAcid (2 μM) and Compounds 187, 138, 119 and 169 on OsteoclastDifferentiation

The differentiation of osteoclast from mouse bone marrow cells wasinduced by using co-culture system, and inhibitory effect of the drug onosteoclast differentiation was evaluated by treatment of single orcombination formulation. Co-culture was performed using mouse-derivedbone marrow cells and osteoblasts.

1. Preparation of Bone Marrow Cells and Osteoblasts

Co-culture was performed using mouse-derived bone marrow cells andosteoblasts.

Femora and tibia were aseptically ectomized from 6˜8 week-old male ddYmice to harvest bone marrow cells by a general method using a syringe.The red blood cells were removed from the bone marrow cells, followed bycentrifugation. The bone marrow cells were suspended in α-MEM mediumsupplemented with 10% fetal bovine serum, and the numbers of theeukaryotic cells in the harvested bone marrow cells were counted andthen immediately used for a co-culture system.

The calvaria were aseptically ectomized from 1˜2 day-old neonatal ICRmice, and osteoblasts were isolated by sequential treatment with anenzyme solution of 0.2% collagenase. The cell suspended supernatant wascentrifuged, and the recovered osteoblasts were propagated in α-MEMmedium supplemented with 10% fetal bovine serum for a predeterminedperiod of time. Then, these cells were diluted to a desired cell number,and used for the experiment.

2. Measurement of Osteoclast Differentiation Via Co-Culture System

The bone marrow cells (1×10⁵ cells/well) and osteoblasts (3,000cells/well) prepared in the above were plated in a 96-well plate usinga-MEM medium supplemented with 10% fetal bovine serum. At this time,differentiation factors, 1α,25-dihydroxyvitamin D₃ (10⁻⁸ M, hereinbelow,referred to as vitamin D₃) and dexamethasone (10⁻⁸ M), were co-added tothe medium to induce osteoclast differentiation. The medium was replacedwith fresh media containing the differentiation factors every 2 to 3days.

After 7 days, when multinucleated osteoclasts were observed, the mediumwas removed from the wells, and then the cells were fixed with PBScontaining 10% Formalin. Tartrate-Resistant Acid Phosphatase(hereinbelow, referred to as TRAP) was used as a marker to measure themature osteoclast in consideration of its characteristics showing apositive reaction to a TRAP staining solution. The TRAP stainingsolution was prepared in such the manner that a substrate, naphtol AS-MSphosphate and a coloring agent (Fast Red Violet LB salt) were dissolvedin N,N-dimethylformamide. A 0.1 N NaHCO₃ buffer solution containing 50mM tartaric acid was added thereto, and the mixture was stored at arefrigerator prior to use as a staining solution. The osteoclasts with6-7 or more nuclei showing a TRAP-positive reaction were counted under amicroscope.

3. Effect of Test Substance on Osteoclast Differentiation

Individual treatment of etidronic acid, Compound 187, Compound 138,Compound 119, or Compound 169 and combination treatment of etidronicacid with Compound 187, Compound 138, Compound 119 or Compound 169 wereperformed to evaluate their effects on osteoclast differentiation by theabove experiment. All experiments were performed using α-MEM mediumsupplemented with 10% fetal bovine serum, containing the differentiationfactors, vitamin D₃ and dexamethasone.

Compound 187, Compound 138, Compound 119 and Compound 169 were dissolvedin DMSO at a concentration of 0.1 mM, and then diluted 1,000 fold withthe differentiation media to a final concentration of 0.1 μM. Etidronicacid was dissolved in purified water at a concentration of 2 mM, andthen diluted 1,000 fold with the media to a final concentration of 2 μM.In this connection, a control group was maintained in 0.1% DMSO.

As the above described, the sample substances and cells, which werediluted to the desired concentrations, were plated in 96-well plate, andco-cultured. On days 3 and 5 of culture, the media were replaced withfresh differentiation media containing the sample substances. On day 7of culture, TRAP staining was performed to count the maturemultinucleated osteoclast that was formed by differentiation. The matureosteoclasts with 6 or more nuclei were counted under a microscope. Theresults were expressed as a percentage (%) of the number of matureosteoclast observed in each experimental group, when the number ofmature osteoclast in the control group (solvent only) was regarded as100%. The experiment was performed with 4 wells per experimental group(n=4), and the results were expressed as mean value±standard deviation.In addition, the experiment was repeated at least three times, andStudent t-test was applied for significant difference betweenexperimental groups. The results are shown in the following Table 2.

TABLE 2 Effect of individual or combination treatment of etidronic acidwith Compound 187, Compound 138, Compound 119, or Compound 169 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Etidronic Compound Compound Compound Compound con(—) acid 187 138119 169 A. Solvent control 100 ± 8.1 group B. Individual 67 ± 7.4* 71 ±6.5* 66 ± 8.3* 78 ± 8.6* treatment of Compound (0.1 μM) C. Individual 86± 6.9* treatment of etidronic acid (2 μM) D. Combination 41 ± 7.5*^(#@)40 ± 8.4*^(#@) 38 ± 8.2*^(#@) 49 ± 9.7*^(#@) treatment of compound +etidronic acid [Note] A. Control group (con(—)): 0.1% DMSO solvent B.Individual treatment of Compounds 187, 138, 119, or 169 (0.1 μM) C.Individual treatment of etidronic acid (2 μM) D. Combination treatmentof etidronic acid (2 μM) with compound 187, 138, 119, or 169 (0.1 μM) *p< 0.0001 vs. solvent control group, ^(#)p < 0.0001 vs. individualtreatment group of each compound ^(@)p < 0.0001 vs. individual treatmentgroup of etidronic acid

As shown in Table 2, when the number of multinucleated osteoclastshowing a TRAP-positive reaction in the solvent control group wasregarded as 100%, the numbers of multinucleated osteoclast, which wereobtained in the individual treatment groups of Compound 187, Compound138, Compound 119 and Compound 169, were expressed as percentage. Wheneach substance was singly added to the co-cultured cells at the sameconcentration of 0.1 μM, the substances showed inhibitory effect onosteoclast differentiation, in which their relative numbers ofmultinucleated osteoclasts to that of the control group was found to be67%, 71%, 66% and 78%, respectively.

In addition, in the experimental group that was singly treated with 2 μMetidronic acid, its relative number of multinucleated osteoclast to thatof the solvent control group was measured as 86%. Such significantreduction indicates that etidronic acid is an osteoclast differentiationinhibitor.

When the combination treatment of etidronic acid with Compound 187,Compound 138, Compound 119 or Compound 169 was simultaneously performed,the relative number of multinucleated osteoclast to that of the solventcontrol group was found to be 41% in the combination treatment group ofetidronic acid with Compound 187. This result indicates that the valueis much lower than the sum of each individual treatment, showing thestrong inhibitory effect on osteoclast differentiation. This notableresult was also observed in the combination treatment of etidronic acidwith Compound 138 (40%), Compound 119 (38%) or Compound 169 (49%). Takentogether, the results demonstrate that the combination treatment of twosubstances exhibited much stronger efficacy than expected from the sumof each individual treatment.

EXAMPLE 2 Effect of Individual or Combination Treatment of ClodronicAcid (1 μM) and Compounds 187, 138, 119 and 169 on OsteoclastDifferentiation

The experiment was performed in the same manner as in Example 1 toevaluate the effect of individual or combination treatment of clodronicacid and Compound 187, Compound 138, Compound 119 and Compound 169 onosteoclast differentiation, except using 1 μM clodronic acid instead of2 μM etidronic acid.

Clodronic acid was dissolved in purified water at a concentration of 1mM, and then diluted 1,000 fold with the media to a final concentrationof 1 μM.

The results are shown in the following Table 3.

TABLE 3 Effect of individual or combination treatment of clodronic acidwith Compound 187, Compound 138, Compound 119, or Compound 169 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Clodronic Compound Compound Compound Compound con(—) acid 187 138119 169 A. Solvent control 100 ± 8.1 group B. Individual 67 ± 7.4* 71 ±6.5* 66 ± 8.3* 78 ± 8.6* treatment of Compound (0.1 μM) C. Individual 88± 9.7* treatment of clodronic acid (1 μM) D. Combination 60 ± 15.2*^(#@)54 ± 11.9*^(#@) 47 ± 13.0*^(#@) 59 ± 14.0*^(#@) treatment of compound +clodronic acid [Note] A. Control group (con(—)): 0.1% DMSO solvent B.Individual treatment of Compounds 187, 138, 119, or 169 (0.1 μM) C.Individual treatment of clodronic acid (1 μM) D. Combination treatmentof clodronic acid (1 μM) with Compounds 187, 138, 119, or 169 (0.1 μM)*p < 0.0001 vs. solvent control group, ^(#)p < 0.0001 vs. individualtreatment group of each compound ^(@)p < 0.0001 vs. individual treatmentgroup of clodronic acid

As mentioned in Example 1, in the experimental group that was singlytreated with Compound 187, Compound 138, Compound or Compound 169, itsrelative number of multinucleated osteoclast to that of the solventcontrol group was found to be significantly low. In the experimentalgroup that was singly treated with 1 μM clodronic acid, its relativenumber of multinucleated osteoclast to that of the solvent control groupwas measured as 88%, resulting in significant reduction (Table 3). Thecombination treatment of the substances was performed in the samemanner. Consequently, a statistically significant increase in theinhibitory effect on osteoclast differentiation was observed in thecombination treatment group of clodronic acid with Compound (54%),Compound 119 (47%) or Compound 169 (59%), except for the combinationtreatment group of clodronic acid with Compound 187.

EXAMPLE 3 Effect of Individual or Combination Treatment of PamidronicAcid (0.1 μM) and Compounds 187, 138, 119 and 169 on OsteoclastDifferentiation

The experiment was performed in the same manner as in Example 1 toevaluate the effect of individual or combination treatment of pamidronicacid and compounds 187, 138, 119 and 169 on osteoclast differentiation,except using μM pamidronic acid instead of 2 μM etidronic acid.

Pamidronic acid was dissolved in purified water at a concentration of0.1 mM, and then diluted 1,000 fold with the media to a finalconcentration of 0.1 μM.

The results are shown in the following Table 4.

TABLE 4 Effect of individual or combination treatment of pamidronic acidwith Compound 187, Compound 138, Compound 119 or Compound 169 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Pamidronic Compound Compound Compound Compound con(—) acid 187138 119 169 A. Solvent control 100 ± 8.1 group B. Individual 67 ± 7.4*71 ± 6.5* 66 ± 8.3* 78 ± 8.6* treatment of Compound (0.1 μM) C.Individual 82 ± 6.7* treatment of pamidronic acid (0.1 μM) D.Combination 47 ± 10.5*^(#@) 42 ± 6.2*^(#@) 37 ± 5.0*^(#@) 50 ± 8.7*^(#@)treatment of compound + pamidronic acid [Note] A. Control group(con(—)): 0.1% DMSO solvent B. Individual treatment of Compounds 187,138, 119, or 169 (0.1 μM) C. Individual treatment of pamidronic acid(0.1 μM) D. Combination treatment of pamidronic acid (0.1 μM) withCompounds 187, 138, 119, or 169 (0.1 μM) *p < 0.0001 vs. solvent controlgroup, ^(#)p < 0.0001 vs. individual treatment group of each compound^(@)p < 0.0001 vs. individual treatment group of pamidronic acid

As shown in Table 4, in the experimental group that was singly treatedwith pamidronic acid (0.1 μM), its relative number of multinucleatedosteoclast to that of the control group was measured as 82%, resultingin significant reduction. As the above mentioned, the combinationtreatment of pamidronic acid with Compound 187, Compound 138, Compound119 or Compound 169 was performed in the same manner. The results are asfollows: 47% in the combination treatment of pamidronic acid withCompound 187, 42% in the combination treatment of pamidronic acid withCompound 138, 37% in the combination treatment of pamidronic acid withCompound 119, and 50% in the combination treatment of pamidronic acidwith Compound 169. In particular, the combination treatment ofpamidronic acid with Compound 138, Compound 119 or Compound 169 showedmuch stronger inhibitory effect, in which the value was about 10% ormore than the sum of each individual treatment.

EXAMPLE 4 Effect of Individual or Combination Treatment of AlendronicAcid (0.2 μM) and Compounds 187, 138, 119 and on OsteoclastDifferentiation

The experiment was performed in the same manner as in Example 1 toevaluate the effect of individual or combination treatment of alendronicacid and compounds 187, 138, 119 and 169 on osteoclast differentiation,except using μM alendronic acid instead of 2 μM etidronic acid.

Alendronic acid was dissolved in purified water at a concentration of0.2 mM, and then diluted 1,000 fold with the media to a finalconcentration of 0.2 μM.

The results are shown in the following Table 5.

TABLE 5 Effect of individual or combination treatment of alendronic acidwith Compound 187, Compound 138, Compound 119, or Compound 169 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Alendronic Compound Compound Compound Compound con(—) acid 187138 119 169 A. Solvent control 100 ± 8.1 group B. Individual 67 ± 7.4*71 ± 6.5* 66 ± 8.3* 78 ± 8.6* treatment of Compound (0.1 μM) C.Individual 80 ± 5.7* treatment of alendronic acid (0.2 μM) D.Combination 32 ± 8.1*^(#@) 32 ± 8.9*^(#@) 29 ± 5.3*^(#@) 44 ± 7.4*^(#@)treatment of compound + alendronic acid [Note] A. Control group(con(—)): 0.1% DMSO solvent B. Individual treatment of Compounds 187,138, 119, or 169 (0.1 μM) C. Individual treatment of alendronic acid(0.2 μM) D. Combination treatment of alendronic acid (0.2 μM) withCompounds 187, 138, 119, or 169 (0.1 μM) *p < 0.0001 vs. solvent controlgroup, ^(#)p < 0.0001 vs. individual treatment group of each compound^(@)p < 0.0001 vs. individual treatment group of alendronic acid

The alendronic acid (0.2 μM) showing a relative value of 80% in itsindividual treatment was treated in combination with Compound 187,Compound 138, Compound 119 or Compound which has the inhibitory effecton osteoclast differentiation. The results are shown in Table 5. Whenthe combination treatment of alendronic acid with Compound 187 thatshowed a relative value of 67% in its individual treatment wassimultaneously performed at the same concentration, the number ofosteoclast was notably reduced as low as 32%. This notable result wasalso observed in the combination treatment of alendronic acid withCompound 138 (32%), Compound 119 (29%) or Compound 169 (44%), indicatingthat the combination treatment of the substances exhibited much strongerefficacy than expected from the sum of each individual treatment.

EXAMPLE 5 Effect of Individual or Combination Treatment of RisedronicAcid (0.1 μM) and Compounds 187, 138, 119 and 169 on OsteoclastDifferentiation

The experiment was performed in the same manner as in Example 1 toevaluate the effect of individual or combination treatment of risedronicacid and Compound 187, Compound 138, Compound 119, or Compound 169 onosteoclast differentiation, except using 0.1 μM risedronic acid insteadof 2 μM etidronic acid.

Risedronic acid was dissolved in purified water at a concentration of0.1 mM, and then diluted 1,000 fold with the media to a finalconcentration of 0.1 μM.

The results are shown in the following Table 6.

TABLE 6 Effect of individual or combination treatment of risedronic acidwith Compound 187, Compound 138, Compound 119, or Compound 169 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Risedronic Compound Compound Compound Compound con(—) acid 187138 119 169 A. Solvent control 100 ± 8.1 group B. Individual 67 ± 7.4*71 ± 6.5* 66 ± 8.3* 78 ± 8.6* treatment of Compound (0.1 μM) C.Individual 82 ± 5.2* treatment of risedronic acid (0.1 μM) D.Combination 40 ± 6.6*^(#@) 35 ± 8.2*^(#@) 38 ± 6.8*^(#@) 42 ± 7.6*^(#@)treatment of compound + risedronic acid [Note] A. Control group(con(—)): 0.1% DMSO solvent B. Individual treatment of Compounds 187,138, 119, or 169 (0.1 μM) C. Individual treatment of risedronic acid(0.1 μM) D. Combination treatment of risedronic acid (0.1 μM) withCompounds 187, 138, 119, or 169 (0.1 μM) *p < 0.0001 vs. solvent controlgroup, ^(#)p < 0.0001 vs. individual treatment group of each compound^(@)p < 0.0001 vs. individual treatment group of risedronic acid

The combination treatment of risedronic acid with four substances wasalso performed to evaluate the inhibitory effect on osteoclastdifferentiation (Table 6). In the individual treatment of 0.1 μMrisedronic acid, the relative number of multinucleated osteoclast wasfound to be about 82%, resulting in significant reduction compared tothe solvent control group. When risedronic acid was added to theco-cultured cells in combination with Compound 187, Compound 138,Compound 119, or Compound 169, the relative numbers of multinucleatedosteoclasts were found to be as low as 40%, 35%, 38 and 42%,respectively. This result has a significant difference from those of thecontrol group and individual treatment groups.

EXAMPLE 6 Effect of Individual or Combination Treatment of IbandronicAcid (0.1 μM) and Compounds 187, 138, 119 and 169 on OsteoclastDifferentiation

The experiment was performed in the same manner as in Example 1 toevaluate the effect of individual or combination treatment of ibandronicacid and Compound 187, Compound 138, Compound 119 and Compound 169 onosteoclast differentiation, except using 0.1 μM ibandronic acid insteadof 2 μM etidronic acid.

Ibandronic acid was dissolved in purified water at a concentration of0.1 mM, and then diluted 1,000 fold with the media to a finalconcentration of 0.1 μM.

The results are shown in the following Table 7.

TABLE 7 Effect of individual or combination treatment of ibandronic acidwith Compound 187, Compound 138, Compound 119, or Compound 169 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Ibandronic Compound Compound Compound Compound con(—) acid 187138 119 169 A. Solvent control 100 ± 8.1 group B. Individual 67 ± 7.4*71 ± 6.5* 66 ± 8.3* 78 ± 8.6* treatment of Compound (0.1 μM) C.Individual 77 ± 8.2* treatment of ibandronic acid (0.1 μM) D.Combination 42 ± 8.1*^(#@) 45 ± 7.6*^(#@) 36 ± 9.8*^(#@) 54 ± 8.7*^(#@)treatment of compound + ibandronic acid [Note] A. Control group(con(—)): 0.1% DMSO solvent B. Individual treatment of Compounds 187,138, 119, or 169 (0.1 μM) C. Individual treatment of ibandronic acid(0.1 μM) D. Combination treatment of ibandronic acid (0.1 μM) withCompounds 187, 138, 119, or 169 (0.1 μM) *p < 0.0001 vs. solvent controlgroup, ^(#)p < 0.0001 vs. individual treatment group of each compound^(@)p < 0.0001 vs. individual treatment group of ibandronic acid

In the individual treatment of ibandronic acid (0.1 μM), a significantreduction (77%) was observed in the number of multinucleated osteoclastshowing a TRAP-positive reaction. In the combination treatment ofibandronic acid with Compound 187, the relative number of multinucleatedosteoclast was found to be 42%, resulting in a significant reductioncompared to that of each individual treatment. As shown in Table 7, thecombination treatment of ibandronic acid with other compounds alsoexhibited a significant reduction in the number of multinucleatedosteoclast.

EXAMPLE 7 Effect of Individual or Combination Treatment of ZoledronicAcid (0.01 μM) and Compounds 187, 138, 119 and 169 on OsteoclastDifferentiation

The experiment was performed in the same manner as in Example 1 toevaluate the effect of individual or combination treatment of zoledronicacid and Compound 187, Compound 138, Compound 119 and Compound 169 onosteoclast differentiation, except using 0.01 μM zoledronic acid insteadof 2 μM etidronic acid.

Zoledronic acid was dissolved in purified water at a concentration of0.01 mM, and then diluted 1,000 fold with the media to a finalconcentration of 0.01 μM.

The results are shown in the following Table 8.

TABLE 8 Effect of individual or combination treatment of zoledronic acidwith Compound 187, Compound 138, Compound 119, or Compound 169 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Zoledronic Compound Compound Compound Compound con(—) acid 187138 119 169 A. Solvent control 100 ± 8.1 group B. Individual 67 ± 7.4*71 ± 6.5* 66 ± 8.3* 78 ± 8.6* treatment of Compound (0.1 μM) C.Individual 84 ± 4.1* treatment of zoledronic acid (0.01 μM) D.Combination 43 ± 4.5*^(#@) 48 ± 8.9*^(#@) 42 ± 8.1*^(#@) 59 ± 8.2*^(#@)treatment of compound + zoledronic acid [Note] A. Control group(con(—)): 0.1% DMSO solvent B. Individual treatment of Compounds 187,138, 119, or 169 (0.1 μM) C. Individual treatment of zoledronic acid(0.1 μM) D. Combination treatment of zoledronic acid (0.01 μM) withCompounds 187, 138, 119, or 169 (0.1 μM) *p < 0.0001 vs. solvent controlgroup, ^(#)p < 0.0001 vs. individual treatment group of each compound^(@)p < 0.0001 vs. individual treatment group of zoledronic acid

The combination treatment of zoledronic acid (0.01 μM) with each of foursubstances that significantly reduced the number of osteoclast was alsoperformed. In the individual treatment of zoledronic acid, a significantreduction (84%) in the number of multinucleated osteoclast was observed.In the combination treatment of zoledronic acid with Compound 187, therelative number of multinucleated osteoclast was found to be 43%, whichis much lower than expected from the sum of each individual treatment.This result also demonstrates that the combination treatment exhibitedsynergistic effect. The combination treatment of zoledronic acid withother compounds was also found to exhibit the same effect (Table 8).

EXAMPLE 8 Effect of Individual or Combination Treatment of AlendronicAcid (0.1 μM) and Benzamidine Derivatives of Formula 1 on OsteoclastDifferentiation

The differentiation of osteoclast from mouse bone marrow cells wasinduced by using co-culture system, and inhibitory effect of the drug onosteoclast differentiation was evaluated by treatment of single orcombination formulation. Co-culture was performed using mouse bonemarrow cells and ST cells of bone marrow-derived stromal cell.

1. Preparation of Bone Marrow Cells and Osteoblasts

Femora and tibia were aseptically ectomized from 6˜8 week-old male ddYmice to harvest bone marrow cells by a general method using a syringe.The red blood cells were removed from the bone marrow cells, followed bycentrifugation. The bone marrow cells were suspended in α-MEM mediumsupplemented with 10% fetal bovine serum, and the numbers of theeukaryotic cells in the harvested bone marrow cells were counted andthen immediately used for a co-culture system.

ST2 cells (RIKEN Cell Bank, Tsukuba, Japan) were cultured in α-MEMmedium supplemented with 10% fetal bovine serum until confluent. Then,these cells were diluted to a desired cell number, and used for theexperiment.

2. Measurement of Osteoclast Differentiation Via Co-Culture System

The bone marrow cells (1×10⁵ cells/well) and ST2 cells (3,000cells/well) prepared in the above were plated in a 96-well plate usingα-MEM medium supplemented with 10% fetal bovine serum. At this time,differentiation factors, 1α,25-dihydroxyvitamin D₃ (10⁻⁸ M, hereinbelow,referred to as vitamin D₃) and dexamethasone (10⁻⁸ M), were co-added tothe medium to induce osteoclast differentiation. The medium was replacedwith fresh media containing the differentiation factors every 2 to 3days.

After 7 days, when multinucleated osteoclasts were observed, the mediumwas removed from the wells, and then the cells were fixed with PBScontaining 10% Formalin. Tartrate-Resistant Acid Phosphatase(hereinbelow, referred to as TRAP) was used as a marker to measure themature osteoclast in consideration of its characteristics showing apositive reaction to a TRAP staining solution. The TRAP stainingsolution was prepared in such the manner that a substrate, naphtol AS-MSphosphate and a coloring agent (Fast Red Violet LB salt) were dissolvedin N,N-dimethylformamide. A 0.1 N NaHCO₃ buffer solution containing 50mM tartaric acid was added thereto, and the mixture was stored at arefrigerator prior to use as a staining solution. The osteoclasts with6-7 or more nuclei showing a TRAP-positive reaction were counted under amicroscope.

3. Effect of Test Substance on Osteoclast Differentiation

Alendronic acid was dissolved in distilled water at a concentration of0.1 mM, and benzamidine derivatives were dissolved in DMSO at aconcentration of 0.1 mM. All of them were diluted 1,000 fold with thedifferentiation media to a final concentration of 0.1 μM, respectively.In this connection, a control group was maintained in 0.1% DMSO.

As the above described, the sample substances and cells, which werediluted to the desired concentrations, were plated in 96-well plate, andco-cultured. On days 3 and 5 of culture, the media were replaced withfresh differentiation media containing the sample substances. On day 7of culture, TRAP staining was performed to count the maturemultinucleated osteoclast that was formed by differentiation. The matureosteoclasts with 6 or more nuclei were counted under a microscope. Theresults were expressed as a percentage (%) of the number of matureosteoclast observed in each experimental group, when the number ofmature osteoclast in the control group (solvent only) was regarded as100%. The experiment was performed with 4 wells per experimental group(n=4), and the results were expressed as mean value±standard deviation.In addition, the experiment was repeated at least two times, and Studentt-test was applied for significant difference between experimentalgroups.

EXAMPLE 9 Effect of Individual or Combination Treatment of RisedronicAcid (0.1 μM) and Benzamidine Derivatives of Formula 1 on OsteoclastDifferentiation

The experiment was performed in the same manner as in Example 8 toevaluate the effect of individual or combination treatment of risedronicacid and benzamidine derivatives of Formula 1 on osteoclastdifferentiation, except using 0.1 μM risedronic acid instead of 0.1 μMalendronic acid.

Risedronic acid was dissolved in distilled water at a concentration of0.1 mM, and then diluted 1,000 fold with the media to a finalconcentration of 0.1 μM.

The Results of Experiments 8 and 9

Individual treatment of Compounds: When the number of multinucleatedosteoclast showing a TRAP-positive reaction in the solvent control groupwas regarded as 100%, the numbers of multinucleated osteoclast, obtainedin the individual treatment groups of benzamidine derivatives of Formula1 were expressed as percentage. When each substance was singly added tothe co-cultured cells at the same concentration of 0.1 μM, thesubstances showed various inhibitory effects on osteoclastdifferentiation.

Individual treatment of alendronic acid or risedronic acid: In theexperimental group that was singly treated with 0.1 μM alendronic acidor risedronic acid, its relative numbers of multinucleated osteoclast tothat of the solvent control group were measured as 76% (alendronic acid)and 69% (risedronic acid). Such significant reduction indicates thatalendronic acid and risedronic acid are inhibitor of osteoclastdifferentiation.

Combination treatment: Effects of combination treatment on osteoclastdifferentiation were evaluated by comparing with those of individualtreatment of Compounds and those of individual treatment of alendronicacid or risedronic acid.

TABLE 9 Effect of individual or combination treatment of alendronic acidor risedronic acid with benzamidine derivatives of Formula 1 onosteoclast differentiation % number of osteoclast (vs. solvent controlgroup) Combination Combination treatment treatment Individual treatment(alendronic acid + (risedronic acid + Compounds (compounds) compounds)compounds) Control 100 ± 9.1  76 ± 6.2* 69 ± 6.7* (DMSO)  3 52 ± 8.9 40± 4.6^(b) 33 ± 6.8^(c)  7 52 ± 4.8 35 ± 7.1^(b) 34 ± 10.1^(c)  8  65 ±10.4 22 ± 3.4^(ab) 27 ± 3.8^(ac)  9 64 ± 3.4 52 ± 15.8 43 ± 2.6^(ac)  1569 ± 5.5 43 ± 11.4 45 ± 9.2^(ac)  21  52 ± 10.4 22 ± 7.1^(ab) 47 ± 10.1 37  68 ± 18.9 30 ± 9.9^(b) 36 ± 14.4^(c)  40 66 ± 7.1 28 ± 4.1^(ab) 20± 3.4^(ac)  41 31 ± 9.4 29 ± 5.0^(b) 31 ± 2.6^(c)  42  69 ± 11.4 33 ±1.9^(ab) 32 ± 8.0^(ac)  43  74 ± 14.6 32 ± 6.6^(ab) 40 ± 7.8^(c)  45 72± 4.6 49 ± 8.1^(ab) 38 ± 11.9^(ac)  46 71 ± 9.4 36 ± 5.1^(ab) 31 ±8.5^(ac)  47 57 ± 7.9 42 ± 4.6^(b) 32 ± 3.0^(ac)  54 41 ± 8.3 20 ±4.1^(ab) 19 ± 4.9^(ac)  59 55 ± 6.5 34 ± 2.2^(ab) 33 ± 5.1^(ac)  67  74± 11.7 53 ± 6.4^(b) 36 ± 1.7^(ac)  68 42 ± 6.9 14 ± 1.4^(ab)  8 ±1.9^(ac)  69  80 ± 11.6 49 ± 7.8^(ab) 44 ± 1.4^(ac)  72 63 ± 1.1 30 ±4.0^(ab) 12 ± 3.2^(ac)  74 60 ± 0.7 36 ± 4.3^(ab) 28 ± 5.4^(ac)  76 53 ±6.5 31 ± 6.8^(ab) 22 ± 3.8^(a)  78 67 ± 2.1 36 ± 4.2^(ab) 20 ± 1.7^(a) 79 44 ± 7.5 22 ± 6.7^(ab) 16 ± 4.0^(ac)  80 65 ± 1.4 42 ± 9.9^(b) 38 ±3.7^(ac)  84 44 ± 4.3 30 ± 5.1^(ab)  6 ± 4.4^(ac)  88 63 ± 7.6 61 ± 11.729 ± 4.7^(ac)  89 58 ± 5.1 38 ± 1.9^(ab) 39 ± 2.7^(ac)  90  87 ± 10.0 54± 8.6^(ab) 39 ± 8.4^(ac)  91 60 ± 8.8 35 ± 2.7^(ab) 32 ± 7.0^(ac)  94 45± 3.0 20 ± 4.8^(ab) 16 ± 3.3^(ac)  95 90 ± 5.4 37 ± 10.3^(ab) 33 ±6.8^(ac)  96 74 ± 8.1 55 ± 10.0 34 ± 7.1^(ac)  97 57 ± 5.2 30 ± 5.7^(ab)13 ± 4.3^(ac)  98 47 ± 3.2 29 ± 1.6^(ab) 11 ± 3.2^(ac) 100 46 ± 8.4 14 ±6.9^(ab) 12 ± 3.0^(ac) 101 50 ± 5.9 24 ± 3.2^(ab) 18 ± 2.8^(ac) 102 47 ±4.0 37 ± 3.6^(b) 21 ± 2.6^(ac) 105  87 ± 11.0 42 ± 3.0^(b) 41 ± 8.8^(ac)109 60 ± 9.6 49 ± 9.8^(b) 30 ± 6.5^(ac) 111  76 ± 12.2 51 ± 6.0 32 ±5.2^(ac) 112 77 ± 9.8 35 ± 7.6^(ab) 31 ± 8.0^(ac) 115  77 ± 12.4 51 ±8.9 45 ± 8.3^(ac) 119 78 ± 9.0 29 ± 4.9^(ab) 29 ± 8.7^(ac) 120 80 ± 6.554 ± 2.4^(ab) 55 ± 9.1^(ac) 121 95 ± 3.9 55 ± 11.1^(ab) 39 ± 5.7^(ac)122 71 ± 4.4 37 ± 8.1^(ab) 49 ± 7.3^(ac) 124 49 ± 3.0 21 ± 4.3^(ab) 17 ±5.2^(ac) 125 66 ± 4.4 43 ± 3.3^(ab) 21 ± 9.0^(ac) 126 50 ± 2.5 23 ±5.8^(ab) 22 ± 2.1^(ac) 127  75 ± 14.3 37 ± 6.8^(ab) 33 ± 7.3^(ac) 132 62± 7.7 37 ± 8.3^(ab) 30 ± 3.4^(ac) 133 54 ± 8.3 42 ± 8.3^(b) 25 ±5.7^(ac) 134 57 ± 4.3 39 ± 3.4^(ab) 24 ± 4.0^(ac) 137 19 ± 2.9 11 ±4.3^(b)  7 ± 2.2^(ac) 138 57 ± 7.2 18 ± 6.8^(ab) 31 ± 3.2^(ac) 139 64 ±4.6 49 ± 7.8 38 ± 6.9^(ac) 141 84 ± 8.8 65 ± 2.8 60 ± 7.5^(ac) 144 82 ±6.7 44 ± 10.5^(ab) 37 ± 4.3^(ac) 146 81 ± 8.9 79 ± 7.8 60 ± 13.6^(c) 14746 ± 4.1 31 ± 3.2^(ab) 14 ± 3.0^(ac) 148 65 ± 4.3 33 ± 8.3^(ab) 19 ±2.4^(a) 149 63 ± 9.9 40 ± 8.8 31 ± 2.5^(ac) 151 58 ± 2.5 36 ± 2.9^(ab)31 ± 3.7 a 152 65 ± 2.2 46 ± 8.8^(b) 48 ± 4.9^(ac) 153 55 ± 3.1 27 ±3.5^(ab) 22 ± 4.5^(ac) 157  78 ± 13.5 39 ± 8.3^(ab) 36 ± 15.1^(ac) 16179 ± 5.1 56 ± 4.3^(ab) 47 ± 14.0^(a) 162 98 ± 8.2 78 ± 1.8 61 ± 7.5^(ac)163 65 ± 8.8 55 ± 7.6 41 ± 7.3^(ac) 165 75 ± 3.8 29 ± 7.5^(ab) 30 ±3.1^(ac) 166 73 ± 4.4 43 ± 9.4^(ab) 35 ± 3.9^(ac) 167 72 ± 9.8 25 ±1.9^(b) 31 ± 7.6^(ac) 168 70 ± 9.1 39 ± 5.2^(ab) 29 ± 9.7^(ac) 172 57 ±5.1 33 ± 5.3^(ab) 26 ± 5.1^(a) 174 70 ± 2.5 46 ± 2.6^(ab) 35 ± 5.1^(ac)177  74 ± 10.1 34 ± 10.2^(ab) 34 ± 5.7^(ac) 182  82 ± 12.0 45 ± 6.7 41 ±5.1^(c) 183 66 ± 7.4 26 ± 6.1^(ab) 37 ± 5.3^(ac) 184 62 ± 4.6 38 ±3.7^(ab) 38 ± 6.9^(ac) 185 81 ± 7.0 57 ± 13.9 45 ± 1.4^(ac) 188 56 ± 5.435 ± 3.2^(ab) 23 ± 5.1^(ac) 193 48 ± 4.4 34 ± 5.0^(ab) 27 ± 4.8^(ac) 194 74 ± 10.1 33 ± 7.1^(ab) 30 ± 7.0^(ac) 196 68 ± 7.1 37 ± 4.6^(ab) 42 ±8.8^(ac) 208 92 ± 5.8 75 ± 6.3 67 ± 6.5^(ac) 209 74 ± 7.4 41 ± 12.0^(ab)50 ± 6.1^(ac) 216 70 ± 5.0 72 ± 13.0 48 ± 7.8^(ac) 218 56 ± 1.9 39 ±10.4^(b) 25 ± 7.5^(ac) 219  61 ± 10.5 51 ± 5.4^(b) 40 ± 3.8^(c) 220 69 ±3.2 53 ± 4.7^(ab) 40 ± 5.1^(ac) 222 74 ± 7.1 49 ± 6.8^(ab) 36 ± 6.6^(ac)223 81 ± 3.8 73 ± 8.2 60 ± 12.6 224 77 ± 8.4 53 ± 2.9^(ab) 58 ± 10.8 22570 ± 7.1 50 ± 4.8^(ab) 48 ± 4.9^(ac) 227 42 ± 4.6 24 ± 5.0^(ab) 17 ±4.4^(ac) 228 49 ± 3.5 31 ± 4.8^(ab) 20 ± 5.8^(ac) 231  82 ± 14.6 50 ±9.8^(b) 40 ± 3.1^(ac) 232 47 ± 9.4 39 ± 5.2^(b) 37 ± 4.9^(c) 234 44 ±7.5 30 ± 6.1^(b) 22 ± 4.0^(ac) 235 38 ± 7.6 33 ± 1.8 25 ± 4.4^(c) 241 61± 6.8 24 ± 4.6^(ab) 12 ± 1.4^(ac) 242 58 ± 3.4 18 ± 3.5^(ab) 13 ±2.8^(ac) 243 36 ± 4.9 24 ± 7.7^(b) 12 ± 2.3^(ac) 244 46 ± 2.9 19 ±3.3^(ab) 11 ± 1.7^(ac) 245 35 ± 5.7 23 ± 4.9^(b) 16 ± 4.1^(ac) 247 63 ±4.2 39 ± 3.7^(ab) 17 ± 4.5^(ac) 248 49 ± 8.7 33 ± 5.6^(b) 27 ± 4.9^(ac)249 36 ± 4.0 24 ± 4.0^(ab) 13 ± 4.8^(ac) 250 52 ± 7.2 45 ± 5.2^(b) 12 ±1.4^(ac) 251 45 ± 9.6 20 ± 6.4^(ab) 18 ± 4.4^(ac) 252 44 ± 2.7 33 ±6.6^(b) 19 ± 4.0^(ac) 254 40 ± 8.3 29 ± 6.3^(b) 11 ± 2.5^(ac) 255 50 ±3.9 18 ± 1.7^(ab) 12 ± 3.1^(ac) 256 49 ± 0.9 26 ± 3.0^(ab) 12 ± 2.4^(ac)262 47 ± 4.2 24 ± 2.6^(ab)  7 ± 4.9^(ac) 266 64 ± 4.0 36 ± 9.6^(ab) 26 ±4.3^(ac) 267 68 ± 8.6 33 ± 5.3^(ab) 13 ± 2.4^(ac) 268 52 ± 9.1 28 ±1.7^(b) 17 ± 3.4^(ac) 269 38 ± 3.7 23 ± 5.2^(ab) 17 ± 4.4^(ac) 270 45 ±6.9 28 ± 4.5^(b) 14 ± 2.1^(ac) 271 30 ± 5.3 13 ± 3.7^(ab) 16 ± 2.9^(ac)273 53 ± 3.4 25 ± 4.5^(ab) 11 ± 2.9^(ac) 274 65 ± 8.9 31 ± 2.9^(ab) 13 ±1.3^(ac) 276  41 ± 12.1 21 ± 2.9^(b) 11 ± 3.1^(c) 280 40 ± 5.0 25 ±6.4^(b)  8 ± 1.4^(ac) 281 30 ± 7.6 22 ± 5.9^(b)  6 ± 2.5^(ac) 282 73 ±7.1 49 ± 9.9^(ab) 45 ± 5.2^(ac) 284 73 ± 7.7 36 ± 5.0^(ab) 19 ± 5.8^(ac)285 70 ± 8.0 53 ± 0.9 40 ± 3.9^(ac) 286 43 ± 6.1 29 ± 4.1^(b) 26 ±1.5^(ac) 289 36 ± 9.1 21 ± 7.4^(b) 10 ± 3.1^(ac) 290 52 ± 6.2 23 ±4.7^(ab) 12 ± 2.0^(ac) 291 44 ± 4.9 20 ± 3.8^(ab) 12 ± 3.5^(ac) 293  36± 10.0 15 ± 2.6^(b) 11 ± 2.6^(c) 294 27 ± 4.5 13 ± 2.4^(ab)  9 ±2.7^(ac) 296 46 ± 3.6 13 ± 2.6^(ab)  8 ± 1.7^(ac) 298 55 ± 6.1 16 ±3.3^(ab)  8 ± 2.9^(ac) 299 40 ± 6.9 14 ± 2.9^(ab) 11 ± 6.0^(ac) 300 48 ±3.0 12 ± 1.7^(ab)  8 ± 5.2^(ac) 301 49 ± 5.1 10 ± 2.3^(ab)  6 ± 2.3^(ac)302  59 ± 10.6 16 ± 4.5^(ab)  9 ± 2.8^(ac) 303  53 ± 10.7 12 ± 2.5^(ab) 8 ± 2.2^(ac) 304 54 ± 6.4 27 ± 6.4^(ab) 16 ± 4.5^(ac) 305 58 ± 6.1 15 ±4.8^(ab) 11 ± 4.1^(ac) 306 48 ± 6.4 18 ± 4.3^(ab) 16 ± 3.3^(ac) 307 43 ±8.9 30 ± 3.0^(b) 16 ± 4.8^(ac) 309 50 ± 6.1 13 ± 5.1^(ab)  8 ± 3.0^(ac)310 49 ± 3.3 33 ± 5.1^(ab) 18 ± 4.5^(ac) 311  46 ± 10.7 21 ± 4.2^(b) 12± 5.8^(ac) 313 53 ± 6.0 23 ± 5.9^(ab) 13 ± 3.3^(ac) 314 43 ± 7.0 15 ±1.7^(ab)  9 ± 3.2^(ac) 317 45 ± 3.2 18 ± 4.6^(ab) 16 ± 3.2^(ac) 318 43 ±3.7 27 ± 3.0^(ab) 12 ± 1.8^(ac) 319 54 ± 5.9 25 ± 2.6^(ab) 11 ± 3.3^(ac)321 48 ± 7.0 19 ± 4.1^(ab) 18 ± 3.0^(ac) 326  46 ± 11.0 34 ± 2.7^(b) 15± 6.0^(ac) 330 46 ± 4.7 23 ± 3.9^(ab) 12 ± 2.4^(ac) 331 43 ± 2.7 18 ±4.6^(ab)  7 ± 1.2^(ac) 335 54 ± 0.9 41 ± 2.0^(ab) 23 ± 5.0^(ac) 336 52 ±4.0 22 ± 3.2^(ab) 16 ± 3.0^(ac) 337 53 ± 3.7 20 ± 3.0^(ab) 16 ± 3.6^(ac)^(a)p < 0.01 vs. individual treatment group of each compound ^(b)p <0.01 vs. individual treatment group of alendronic acid ^(c)p < 0.01 vs.individual treatment group of risedronic acid

INDUSTRIAL APPLICABILITY

A pharmaceutical composition according to the present invention whichcomprises benzmidine derivatives or salt thereof, is useful for theprevention and treatment of osteoporosis.

1. A method of treating or preventing osteoporosis comprisingadministering to a patient in need thereof an effective amount ofpharmaceutical composition comprising the following compounds (a) and(b) for the purpose of using simultaneously, separately, or sequentiallyas active ingredients: (a) a benzamidine derivative represented by thefollowing Formula 1 or salt thereof, and (b) bisphosphonate representedby the following Formula 2,

wherein R₁ is C₁˜C₆ alkyl which is unsubstituted or substituted withpyridinyl; straight or branched C₁˜C₆ alkyl which is substituted with

unsubstituted or substituted with hydroxy; C₃˜C₆ cycloalkyl; phenyl;benzyl; pyridinyl which is unsubstituted or substituted with C₁˜C₆alkyl; guanidino; NR₆R₇; CH₂NR₆R₇;

group which is substituted with straight or branched C₁˜C₆ alkyl; or

(wherein A is C₁˜C₆ alkyl, and m is an integer of 2 to 6); R₂ ishydrogen; straight or branched C₁˜C₆ alkyl which is unsubstituted orsubstituted with NR₈R₉; C₃˜C₆ cycloalkyl; phenyl; benzyl; C₂˜C₆ alkenyl;carbonyl which is substituted with NR₈R₉; amino; dimethylamino;morpholinyl; thiomorpholinyl; 4-methylpiperazinyl; or straight orbranched C₁˜C₆ alkyl which is substituted with hydroxy, C₁˜C₆ alkoxy,halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl; R₃ and R₄ are each independently hydrogen;halogen; hydroxy; C₁˜C₆ alkyl which is unsubstituted or substituted withhalogen; C₃˜C₆ cycloalkylamino; C₁˜C₆ alkoxy; C₁˜C₆ alkanoyloxy; C₂˜C₆alkenyloxy; phenyl-C₁˜C₆ alkoxy; phenoxy; C₂˜C₆ alkenoyloxy orphenyl-C₁˜C₆ alkanoyloxy; C₃˜C₆ cycloalkyloxy which is substituted withone group selected from carboxy, esterified carboxy and amidatedcarboxy; or an aminooxy group; R₅ is hydrogen or hydroxy group; R₆ andR₇ are each independently hydrogen; C₁˜C₆ alkyl which is unsubstitutedor substituted with one group selected from hydroxy, C₁˜C₆ alkoxy,pyridine and

phenyl; benzyl; pyridinyl; carbonyl which is substituted with one groupselected from C₁˜C₆ alkyl, hydroxy, C₁˜C₆ alkyl substituted withhydroxy, C₁˜C₆ alkoxy, phenyl, benzyl, pyridine and

or C₁˜C₆ alkanesulfonyl; R₈ and R₉ are each independently hydrogen;C₁˜C₆ alkyl which is unsubstituted or substituted with one groupselected from hydroxy, C₁˜C₆ alkoxy, morpholine, imidazole and NR₆R₇;C₁˜C₆ alkoxy; C₃˜C₆ cycloalkyl; phenyl; benzyl; pyridinyl; morpholine;carbonyl which is substituted with one group selected from C₁˜C₆ alkyl,C₁˜C₆ alkoxy, phenyl, benzyl, pyridine and

carbonyl which is substituted with C₁˜C₆ alkyl substituted with onegroup selected from halogen, C₁˜C₆ alkoxy and imidazole; or C₁˜C₆alkanesulfonyl; R₁₀ and R₁₁ are each independently hydrogen, C₁˜C₂alkyl, C₁˜C₃ alkoxy or halide; X₁ and X₃ are each independently O; S;NH; or N—C₁˜C₆ alkyl, N—C₃˜C₆ cycloalkyl, N-benzyl or N-phenyl group; X₂is C₃˜C₇ alkylene; C₁˜C₃ alkylene-C₂˜C₇ alkenylene-C₁˜C₃ alkylene; C₁˜C₃alkylene-O—C₁˜C₃ alkylene; C₁˜C₃ alkylene-S—C₁˜C₃ alkylene; C₁˜C₃alkylene-NH—C₁˜C₃ alkylene; C₁˜C₃ alkylene-phenylene-C₁-C₃ alkylene;C₁-C₃ alkylene-pyridyiene-C₁-C₃ alkylene or C₁-C₃alkylene-naphthylene-C₁˜C₃ alkylene; C₃˜C₇ alkylene which is substitutedwith C₁˜C₃ alkyl and hydroxyl; C₃˜C₇ alkylene carbonyl; or C₃˜C₇alkylene which is interrupted by piperazine; Y is O, S, NR₆ or CH₂group; and n is an integer of 0, 1 and 2,

wherein R₁₂ is methyl, chloro, 2-aminoethyl, 3-aminopropyl,4-aminobutyl, 5-aminopentyl, 4-chlorophenylthio, 3-pyridylmethyl,(imidazo[1,2-a]pyridine-3-yl)methyl, 2-(N-methyl-N-n-pentyl)aminoethyl,cycloheptylamino, (1-imidazolyl)methyl or 1-pyrrolidinylethyl, R₁₃ ishydrogen, chloro or hydroxy group, M is hydrogen or sodium, and Z is anynumber, preferably an integer of 0 to
 7. 2. The method of claim 1,wherein the R₁ is C₁˜C₅ alkyl; C₁˜C₅ alkyl substituted with piperidinyl;C₃˜C₆ cycloalkyl; phenyl; pyridinyl; guanidino; NR₆R₇; piperidinyl orpiperazinyl substituted with straight C₁˜C₃ alkyl; morpholinyl; orpiperidinyl; the R₂ is hydrogen; straight or branched C₁˜C₄ alkyl whichis unsubstituted or substituted with NR₈R₉; C₃˜C₆ cycloalkyl; benzyl;C₂˜C₆ alkenyl; carbonyl which is substituted with NR₈R₉; amino;dimethylamino; morpholinyl; thiomorpholinyl; 4-methylpiperazinyl; orstraight or branched C₁˜C₃ alkyl which is substituted with C₁˜C₃ alkoxy,halogen, C₃˜C₆ cycloalkyl, morpholinyl, dimethylmorpholinyl,thiomorpholinyl, 4-methylpiperazinyl, piperidinyl, imidazolyl, orpyrrolidinyl, the R₃ is hydrogen, the R₄ is hydrogen, hydroxy or fluoro,the R₅ is hydrogen or hydroxy; the R₆ and R₇ are each independentlyhydrogen; C₁˜C₃ alkyl which is unsubstituted or substituted with onegroup selected from hydroxy, C₁˜C₃ alkoxy, pyridinyl, morpholinyl andpiperidinyl; benzyl; carbonyl which is substituted with one groupselected from C₁˜C₃ alkyl, C₁˜C₃ alkyl substituted with hydroxy andpyridinyl; or C₁˜C₃ alkanesulfonyl; the R₈ and R₉ are each independentlyhydrogen; C₁˜C₄ alkyl which is unsubstituted or substituted with onegroup selected from hydroxy, C₁˜C₃ alkoxy, morpholinyl and imidazolyl;C₃˜C₆ cycloalkyl; benzyl; or pyridinoyl; and the X₁—X₂—X₃ is


3. The method of claim 2, wherein the R₁ is methyl; ethyl; isopropyl;tert-butyl; pentyl; piperidin-1-ylmethyl; cyclohexyl; phenyl;pyridin-3-yl; guanidino; NR₆R₇; 1-propyl-piperidin-4-yl;4-methyl-piperazin-1-yl; morpholin-4-yl; or piperidin-4-yl; the R₂ ishydrogen; methyl, ethyl, propyl, isopropyl or butyl which isunsubstituted or substituted with NR₈R₉; cyclopentyl; benzyl; ehthenyl;carbonyl which is substituted with NR₈R₉; amino; dimethylamino;morpholin-4-yl; thiomorpholin-4-yl; 4-methylpiperazin-1-yl; or straightor branched C₁˜C₃ alkyl which is substituted with methoxy, chloro,cyclopentyl, morpholin-4-yl, 2,6-dimethylmorpholin-4-yl,thiomorpholin-4-yl, 4-methylpiperazin-1-yl, piperidin-1-yl,imidazol-1-yl, or pyrrolidin-1-yl; the R₆ and R₇ are each independentlyhydrogen; methyl; ethyl; propyl; C₁˜C₃ alkyl which is substituted withone group selected from hydroxy, methoxy, pyridin-3-yl, pyridin-4-yl,morpholin-4-yl and piperidin-1-yl; benzyl; carbonyl which is substitutedwith one group selected from isopropyl, hydroxymethyl, pyridin-3-yl andpyridin-4-yl; or ethanesulfonyl; and the R₈ and R₉ are eachindependently hydrogen; methyl; ethyl; propyl; isopropyl; butyl;isobutyl; tert-butyl; C₁˜C₃ alkyl which is substituted with one groupselected from hydroxy, methoxy, isopropoxy, morpholin-4-yl andimidazol-1-yl; cyclopropyl; cyclohexyl; benzyl; 3-pyridinoyl or4-pyridinoyl.
 4. The method of claim 2, wherein the only one between theR₆ and the R₇ is hydrogen.
 5. The method of claim 2, wherein the R₆ andR₇ are both hydrogen; or C₁˜C₆ alkyl which is unsubstituted orsubstituted with one group selected from hydroxy, C₁˜C₆ alkoxy andpyridinyl.
 6. The method of claim 5, wherein the R₆ and R₇ are bothhydrogen; methyl; methyl substituted with pyridinyl; ethyl; ethylsubstituted with hydroxy or methoxy; or propyl.
 7. The method of claim2, wherein the R₆ is methyl; and the R₇ is C₁˜C₆ alkyl which isunsubstituted or substituted with one group selected from hydroxy, C₁˜C₆alkoxy, pyridinyl and morpholinyl; benzyl; or carbonyl which issubstituted with C₁˜C₆ alkyl.
 8. The method of claim 7, wherein the R₇is methyl which is substituted with pyridin-3-yl or pyridin-4-yl; ethylwhich is unsubstituted or substituted with one group selected fromhydroxy, methoxy and morpholin-4-yl; benzyl; carbonyl which issubstituted with isopropyl.
 9. The method of claim 2, wherein the R₆ isethyl; and the R₇ is C₁˜C₆ alkyl which is unsubstituted or substitutedwith hydroxy or morpholinyl; or benzyl.
 10. The method of claim 9,wherein the R₇ is ethyl which is substituted with hydroxy ormorpholinyl; or benzyl.
 11. The method of claim 2, wherein the only onebetween the R₈ and the R₉ is hydrogen.
 12. The method of claim 2,wherein the R₈ and R₉ are both C₁˜C₆ alkyl which is unsubstituted orsubstituted with hydroxy.
 13. The method of claim 12, wherein the R₈ andR₉ are both ethyl, hydroxyethyl or propyl.
 14. The method of claim 2,wherein the R₈ is C₃˜C₆ cycloalkyl; and the R₉ is carbonyl substitutedwith pyridinyl.
 15. The method of claim 14, wherein the R₉ is3-pyridinoyl or 4-pyridinoyl.
 16. The method of claim 1, wherein the R₁is C₁˜C₆ alkyl which is unsubstituted or substituted with pyridinyl; andthe R₂ is hydrogen; straight or branched C₁˜C₆ alkyl which isunsubstituted or substituted with NR₈R₉; C₃˜C₆ cycloalkyl; C₂˜C₆alkenyl; carbonyl which is substituted with NR₈R₉; amino; dimethylamino;morpholinyl; or straight or branched C₁˜C₆ alkyl which is substitutedwith hydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.
 17. The method of claim 1, wherein the R₁is straight or branched C₁˜C₆ alkyl which is substituted with

unsubstituted or substituted with hydroxyl; and the R₂ is straight orbranched C₁˜C₆ alkyl which is substituted with hydroxy, C₁˜C₆ alkoxy,halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.
 18. The method of claim 1, wherein the R₁is C₃˜C₆ cycloalkyl; and the R₂ is hydrogen; straight or branched C₁˜C₆alkyl which is unsubstituted or substituted with NR₈R₉; or straight orbranched C₁˜C₆ alkyl which is substituted with hydroxy, C₁˜C₆ alkoxy,halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.
 19. The method of claim 1, wherein the R₁is phenyl or benzyl; and the R₂ is phenyl; benzyl; amino; or straight orbranched C₁˜C₆ alkyl which is substituted with hydroxy, C₁˜C₆ alkoxy,halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.
 20. The method of claim 1, wherein the R₁is pyridinyl which is unsubstituted or substituted with C₁˜C₆ alkyl; andthe R₂ is hydrogen; straight or branched C₁˜C₆ alkyl which isunsubstituted or substituted with NR₈R₉; phenyl; benzyl; C₂˜C₆ alkenyl;or straight or branched C₁˜C₆ alkyl which is substituted with hydroxy,C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.
 21. The method of claim 1, wherein the R₁is guanidino; and the R₂ is straight or branched C₁˜C₆ alkyl which isunsubstituted or substituted with NR₈R₉.
 22. The method of claim 1,wherein the R₁ is NR₆R₇ or CH₂NR₆R₇; and the R₂ is hydrogen; straight orbranched C₁˜C₆ alkyl which is unsubstituted or substituted with NR₈R₉;C₃˜C₆ cycloalkyl; C₂˜C₆ alkenyl; carbonyl which is substituted withNR₈R₉; or straight or branched C₁˜C₆ alkyl which is substituted withhydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.
 23. The method of claim 1, wherein the R₁is

group which is substituted with straight or branched C₁˜C₆ alkyl; andthe R₂ is straight or branched C₁˜C₆ alkyl which is unsubstituted orsubstituted with NR₈R₉; C₃˜C₆ cycloalkyl; morpholinyl; thiomorpholinyl;4-methylpiperazinyl; or straight or branched C₁˜C₆ alkyl which issubstituted with hydroxy, C₁˜C₆ alkoxy, halogen, C₃˜C₆ cycloalkyl,

imidazolyl, or pyrrolidinyl.
 24. The method of claim 1, wherein thecompound of Formula 1 is selected from the group consisting of: 1)N-hydroxy-4-{5-[4-(2-isopropyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,2)4-{5-[4-(2-isopropyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,3)N-hydroxy-4-{5-[4-(2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,4)N-hydroxy-4-{5-[4-(2-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,5)N-hydroxy-4-{5-[4-(2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,6)N-hydroxy-4-{5-[4-(2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,7)N-hydroxy-4-{5-[4-(2-pyridine-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,8)N-hydroxy-4-{5-[4-(2-cyclohexyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,9)N-hydroxy-4-{5-[4-(2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,10)N-hydroxy-4-{5-[4-(2,5-dimethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,11)N-hydroxy-4-{5-[4-(2-ethyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,12)N-hydroxy-4-{5-[4-(5-methyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,13)N-hydroxy-4-{5-[4-(5-methyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,14)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,15)N-hydroxy-4-{5-[4-(5-methyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,16)N-hydroxy-4-{5-[4-(2-t-butyl-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,17)N-hydroxy-4-{5-[4-(5-ethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,18)N-hydroxy-4-{5-[4-(2,5-diethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,19)N-hydroxy-4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,20)N-hydroxy-4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,21)N-hydroxy-4-{5-[4-(5-ethyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,22)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,23)N-hydroxy-4-{5-[4-(5-ethyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,24)N-hydroxy-4-{5-[4-(2-ethyl-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,25)N-hydroxy-4-{5-[4-(2,5-diisopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,26)N-hydroxy-4-{5-[4-(5-isopropyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,27)N-hydroxy-4-{5-[4-(5-isopropyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,28)N-hydroxy-4-{5-[4-(5-isopropyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,29)N-hydroxy-4-{5-[4-(2-methyl-5-propyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,30)N-hydroxy-4-{5-[4-(5-butyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,31)N-hydroxy-4-{5-[4-(5-butyl-2-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,32)N-hydroxy-4-{5-[4-(5-butyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,33)N-hydroxy-4-{5-[4-(5-butyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,34)N-hydroxy-4-{5-[4-(5-butyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,35)N-hydroxy-4-{5-[4-(5-butyl-2-cyclohexyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,36)N-hydroxy-4-{5-[4-(5-butyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,37)N-hydroxy-4-{5-[4-(5-butyl-2-t-butyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,38)N-hydroxy-4-{5-[4-(5-benzyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,39)N-hydroxy-4-{5-[4-(5-benzyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,40)N-hydroxy-4-{5-[4-(5-benzyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,41)N-hydroxy-4-{5-[4-(5-benzyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,42)N-hydroxy-4-{5-[4-(5-(2-chloro-ethyl)-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,43)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,44)N-hydroxy-4-{5-[4-(5-isobutyl-2-methyl-1,3-thiazole-4-yl)phenoxy]pentyloxy}-benzamidine,45)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,46)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,47)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,48)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,49)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-pyridin-3-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,50)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-cyclohexyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,51)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-pentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,52) 4-{5-[4-(2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,53)4-{5-[4-(2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,54)4-{5-[4-(2,5-dimethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,55)4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,56)4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,57)N-hydroxy-4-{5-[4-(2-amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,58)N-hydroxy-4-{5-[4-(2-amino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,59)N-hydroxy-4-{5-[4-(2-guanidino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,60)N-hydroxy-4-{5-[4-(2-amino-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,61)N-hydroxy-4-{5-[4-(2-amino-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,62)N-hydroxy-4-{5-[4-(2-guanidino-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,63)N-hydroxy-4-{5-[4-(2-amino-5-butyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,64)N-hydroxy-4-{5-[4-(5-butyl-2-guanidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,65)N-hydroxy-4-{5-[4-(2-amino-5-benzyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,66)N-hydroxy-4-{5-[4-(5-benzyl-2-guanidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,67)N-hydroxy-4-{5-[4-(2-amino-5-cyclopentylmethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,68)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(1-propyl-piperidin-4-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,69)N-hydroxy-4-{5-[4-(2-(isobutyryl)amino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,70)N-hydroxy-4-{5-[4-(5-isopropyl-2-morpholinomethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,71)N-hydroxy-4-{5-[4-(2-aminomethyl-5-benzyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,72)N-hydroxy-4-{5-[4-(5-methyl-2-(1-propyl-piperidin-4-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,73)N-hydroxy-4-{5-[4-(5-isopropyl-2-aminomethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,74)N-hydroxy-4-{5-[4-(5-vinyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,75)N-hydroxy-4-{5-[4-(5-hydroxymethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,76)N-hydroxy-4-{5-[4-(5-methoxymethyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,77)N-hydroxy-4-{5-[4-(5-(2-chloroethyl)-2-amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,78)N-hydroxy-4-{5-[4-(5-vinyl-2-amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,79)N-hydroxy-4-{5-[4-(5-vinyl-2-(pyridin-3-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,80)N-hydroxy-4-{5-[4-(5-(2-chloroethyl)-2-(pyridin-3-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,81)N-hydroxy-4-{5-[4-(2-amino-5-cyclopentyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,82)N-hydroxy-4-{5-[4-(5-ethyl-2-aminomethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,83)N-hydroxy-4-{5-[4-(5-isopropyl-2-(piperidin-3-yl)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,84)N-hydroxy-4-{5-[4-(2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,85)N-hydroxy-4-{5-[4-(2-ethanesulphonylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,86)N-hydroxy-4-{5-[4-(5-methyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,87)N-hydroxy-4-{5-[4-(2-ethylamino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,88)N-hydroxy-4-{5-[4-(5-methyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,89)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,90)N-hydroxy-4-{5-[4-(2-hydroxyacetylamino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,91)N-hydroxy-4-{5-[4-(5-methyl-2-(4-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,92)N-hydroxy-4-{5-[4-(5-methyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,93)N-hydroxy-4-{5-[4-(2-ethanesulphonylamino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,94)N-hydroxy-4-{5-[4-(2-(2-methoxyethyl)amino-5-methyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,95)N-hydroxy-4-{5-[4-(2-ethanesulphonylamino-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,96)N-hydroxy-4-{5-[4-(5-ethyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,97)N-hydroxy-4-{5-[4-(5-ethyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,98)N-hydroxy-4-{5-[4-(5-ethyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,99)N-hydroxy-4-{5-[4-(5-ethyl-2-methoxyacetylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,100)N-hydroxy-4-{5-[4-(5-ethyl-2-(4-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,101)N-hydroxy-4-{5-[4-(5-ethyl-2-(3-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,102)N-hydroxy-4-{5-[4-(5-ethyl-2-(2-methoxyethyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,103)N-hydroxy-4-{5-[4-(5-isopropyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,104)N-hydroxy-4-{5-[4-(2-ethylamino-5-isopropyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,105)N-hydroxy-4-{5-[4-(5-butyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,106)N-hydroxy-4-{5-[4-(5-butyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,107)N-hydroxy-4-{5-[4-(5-benzyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,108)N-hydroxy-4-{5-[4-(5-benzyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,109)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,110)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-ethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,111)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,112)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-(4-pyridylcarbonyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,113)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-propylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,114)N-hydroxy-4-{5-[4-(5-isopropyl-2-[(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,115)N-hydroxy-4-{5-[4-(5-(2-chloroethyl)-2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,116)N-hydroxy-4-{5-[4-(2-methylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,117)N-hydroxy-4-{5-[4-(5-ethyl-2-(pyridin-3-ylmethyl)amino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,118)N-hydroxy-4-{5-[4-(2-(ethanesulphonyl-methyl-amino)-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,119)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,120)N-hydroxy-4-[5-(4-{2-[(2-hydroxyethyl)-methyl-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,121)N-hydroxy-4-[5-(4-{2-[ethyl-(2-hydroxyethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,122)N-hydroxy-4-[5-(4-{2-[bis-(2-methoxyethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,123)N-hydroxy-4-[5-(4-{5-methyl-2-[methyl-(2-morpholinoethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,124)N-hydroxy-4-[5-(4-{2-[ethyl-1-(2-morpholinoethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,125)N-hydroxy-4-{5-(4-[2-(benzyl-methyl-amino)-5-methyl-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,126)N-hydroxy-4-[5-{4-[5-methyl-2-(methyl-pyridin-3-yl-methyl-amino)-1,3-thiazol-4-yl]phenoxy}pentyloxy]-benzamidine,127)N-hydroxy-4-[5-{4-[2-(benzyl-ethyl-amino)-5-methyl-1,3-thiazol-4-yl]phenoxy}pentyloxy]-benzamidine,128)N-hydroxy-4-[5-(4-{2-[bis-(2-hydroxyethyl)-amino]-5-methyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,129)N-hydroxy-4-[5-(4-{5-ethyl-2-[(2-hydroxyethyl)-methyl-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,130)N-hydroxy-4-[5-(4-{5-ethyl-2-[ethyl-(2-hydroxyethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,131)N-hydroxy-4-[5-(4-{5-ethyl-2-[methyl-(2-morpholinoethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,132)N-hydroxy-4-[5-(4-{5-ethyl-2-[ethyl-(2-morpholinoethyl)-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,133)N-hydroxy-4-[5-{4-[2-(benzyl-methyl-amino)-5-ethyl-1,3-thiazol-4-yl]phenoxy}pentyloxy]-benzamidine,134)N-hydroxy-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,135)N-hydroxy-4-(5-{4-[2-(benzyl-ethyl-amino)-5-ethyl-1,3-thiazol-4-yl]phenoxy}pentyloxy)-benzamidine,136)N-hydroxy-4-{5-(4-[5-ethyl-2-(ethyl-[pyridin-3-ylmethyl]amino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,137)N-hydroxy-4-[5-(4-{2-[bis-(pyridin-3-ylmethyl)amino]-5-ethyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,138)N-hydroxy-4-{5-[4-(2-dipropylamino-5-ethyl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,139)N-hydroxy-4-[5-(4-{2-[bis-(2-hydroxyethyl)amino]-5-ethyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,140)N-hydroxy-4-[5-(4-{2-[(2-hydroxyethyl)-methyl-amino]-5-isopropyl-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,141)N-hydroxy-4-[5-(4-{5-isopropyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,142)N-hydroxy-4-(5-{4-[2-(ethanesulphonyl-methyl-amino)-5-isopropyl-1,3-thiazol-4-yl]phenoxy}pentyloxy)-benzamidine,143)N-hydroxy-4-[5-(4-{5-butyl-2-[(2-hydroxyethyl)-methyl-amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,144)N-hydroxy-4-[5-(4-{5-butyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,145)N-hydroxy-4-[5-(4-{5-butyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,146)N-hydroxy-4-{5-[4-(5-butyl-2-dipropylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,147)N-hydroxy-4-[5-(4-{5-cyclopentylmethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,148)N-hydroxy-4-[5-(4-{5-cyclopentylmethyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,149)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-dipropylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,150)N-hydroxy-4-{5-[4-(5-butyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,151)N-hydroxy-4-{5-[4-(5-butyl-2-ethylmethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,152)N-hydroxy-4-{5-[4-(5-butyl-2-dimethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,153)N-hydroxy-4-[5-(4-{5-cyclopentyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,154)N-hydroxy-4-[5-(4-{5-isobutyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,155)N-hydroxy-4-(5-{4-[5-(2-chloroehtyl)-2-dimethylamino-1,3-thiazol-4-yl]phenoxy}pentyloxy)-benzamidine,156)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,157)N-hydroxy-4-{5-[4-(5-isopropyl-2-dipropylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,158)N-hydroxy-4-{5-[4-(5-ethyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,159)N-hydroxy-4-[5-(4-{5-isopropyl-2-[methyl-(2-morpholinoethyl)amino]-1,3-thiazol-4-yl}phenoxy)pentyloxy]-benzamidine,160)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,161)N-hydroxy-4-{5-[4-(5-isopropyl-2-dimethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,162)N-hydroxy-4-{5-[4-(5-isopropyl-2-diethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,163)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-dimethylamino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,164)N-hydroxy-4-{5-[4-(5-methyl-2-piperidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,165)N-hydroxy-4-{5-[4-(5-methyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,166)N-hydroxy-4-{5-[4-(5-ethyl-2-piperidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,167)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-piperidino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,168)N-hydroxy-4-{5-[4-(5-cyclopentylmethyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,169)N-hydroxy-4-{5-[4-(5-isopropyl-2-morpholino-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,170)N-hydroxy-4-{5-(4-[5-cyclopentylmethyl-2-(4-methylpiperazino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,171)N-hydroxy-4-{5-[4-(5-vinyl-2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,172)N-hydroxy-4-{5-[4-(5-cyclopentyl-2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,173)N-hydroxy-4-{5-[4-(5-isobutyl-2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,174)N-hydroxy-4-{5-(4-[5-ethyl-2-(4-methylpiperazino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,175)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentyloxy}-benzamidine,176)N-hydroxy-4-{5-(4-[5-isopropyl-2-(4-methylpiperazino)-1,3-thiazol-4-yl]phenoxy)pentyloxy}-benzamidine,177)N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentylamino}-benzamidine,178)N-hydroxy-4-(2-{2-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-ethoxy}-ethoxy)-benzamidine,179)N-hydroxy-4-{3-hydroxy-5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-3-methyl-pentyloxy}-benzamidine,180)N-hydroxy-4-(2-{2-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-1-methyl-ethylamino}-ethoxy)-benzamidine,181)N-hydroxy-4-[3-(4-{3-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-propyl}-piperazine-1-yl)-propoxy]-benzamidine,182)N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentanoyl-amino}-benzamidine,183)N-hydroxy-4-({5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyl}-methyl-amino)-benzamidine,184)N-hydroxy-4-{4-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-but-2-enyloxy}-benzamidine,185)N-hydroxy-4-{4-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,186)N-hydroxy-4-(2-{2-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)phenoxy]-ethylamino}-ethoxy)-benzamidine,187)N-hydroxy-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,188)2,N-dihydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,189)N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-3-methoxy-benzamidine,190)N-hydroxy-2-cyclohexylamino-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,191)N-hydroxy-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,192)N-hydroxy-2-fluoro-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,193)N-hydroxy-4-{3-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)phenoxy]propoxy}-benzamidine,194)N-hydroxy-4-{4-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)phenoxy]butoxy}-benzamidine,195)N-hydroxy-3-{5-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxy]-pentylamino}-benzamidine,196)N-hydroxy-4-{4-[4-(2-cyclohexyl-5-ethyl-thiazol-4-yl)-phenoxy]-butoxy}-benzamidine,197)N-hydroxy-4-[3-(4-{5-ethyl-2-[(2-hydroxyethyl)-methyl-amino]-thiazol-4-yl}phenoxy)propoxy]-benzamidine,198)N-hydroxy-4-[4-(4-{5-ethyl-2-[(2-hydroxyethyl)-methyl-amino]-thiazol-4-yl}phenoxy)butoxy]-benzamidine,199)N-hydroxy-4-[3-(4-{5-ethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-thiazol-4-yl}phenoxy)propoxy]-benzamidine,200)N-hydroxy-4-[4-(4-{5-ethyl-2-[methyl-(pyridin-3-ylmethyl)amino]-thiazol-4-yl}phenoxy)butoxy]-benzamidine,201)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-isopropyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,202)N-hydroxy-4-{4-[4-(5-butyl-2-isopropyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,203)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-amino-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,204)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-amino-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-2-fluoro-benzamidine,205)N-hydroxy-4-{4-[4-(2-methylamino-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,206)N-hydroxy-4-{6-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxymethyl]-pyridine-2-yl-methoxy}-benzamidine,207)N-hydroxy-2-fluoro-4-{4-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxy]-butoxy}-benzamidine,208)N-hydroxy-4-{2-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,209)N-hydroxy-4-{3-[4-(5-isopropyl-2-methyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,210)N-hydroxy-4-{4-[4-(5-cyclopentylmethyl-2-cyclohexyl-thiazol-4-yl)-phenoxymethyl]-benzyloxy}-benzamidine,211)N-hydroxy-4-{6-[4-(5-isopropyl-2-methyl-thiazol-4-yl)phenoxy]-hexyloxy}-benzamidine,212)N-hydroxy-4-{5-[2-ethyl-5-hydroxy-4-(2-methyl-thiazol-4-yl)phenoxy]-pentyloxy}-benzamidine,213)N-hydroxy-4-{5-[2-ethyl-4-(2-methyl-thiazol-4-yl)-5-propoxy-phenoxy]-pentyloxy}-benzamidine,214)N-hydroxy-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,215)4-(5-{4-[5-(2-isobutylaminoethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,216)N-hydroxy-4-(5-{4-[2-methyl-5-(2-piperidin-1-yl-ethyl)-thiazole-4-yl]-phenoxy}-pentyloxy)-benzamidine,217)N-hydroxy-4-[5-(4-{2-methyl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,218)N-hydroxy-4-[5-(4-{5-[2-(3-imidazol-1-yl-propylamino)-ethyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,219)N-hydroxy-4-(5-{4-[5-(2-isopropylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,220)N-hydroxy-4-[5-(4-{5-[2-(3-isopropoxy-propylamino)-ethyl]-2-methyl-thiazole-4-yl}-phenoxy)-pentyloxy]-benzamidine,221)N-hydroxy-4-(5-{4-[5-(2-butylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,222)N-hydroxy-4-(5-{4-[5-(2-imidazol-1-yl-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,223)N-hydroxy-4-(5-{4-[5-(2-cyclohexylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,224)N-hydroxy-4-(5-{4-[5-(2-diethylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,225)N-hydroxy-4-{5-[4-(5-{2-[bis-(2-hydroxy-ethyl)-amino]-ethyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,226)N-hydroxy-4-(5-{4-[5-(2-diisopropylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,227) N-hydroxy-4-[5-(4-{5-[2-(2,6-dimethyl-morpholin-4-yl)-ethyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine, 228)N-hydroxy-4-(5-{4-[2-methyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,229)N-hydroxy-4-(5-{4-[2-amino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,230)N-hydroxy-4-[5-(4-{5-[2-(2-dimethylamino-ethylamino)-ethyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,231)N-hydroxy-4-(5-{4-[2-methyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,232)N-hydroxy-4-[5-(4-{2-methyl-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-yl}-phenoxy)-pentyloxy]-benzamidine,233)N-hydroxy-4-{5-[4-(5-{2-[bis-(2-methoxy-ethyl)-amino]-ethyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,234)N-hydroxy-4-(5-{4-[5-(2-tert-butylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,235)N-hydroxy-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,236)N-hydroxy-4-(5-{4-[5-(2-morpholin-4-yl-ethyl)-2-pyridin-3-yl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,237)N-hydroxy-4-[5-(4-{5-[2-(4-methyl-piperazin-1-yl)-ethyl]-2-pyridin-3-yl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,238)N-hydroxy-4-(5-{4-[2-pyridin-3-yl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,239)N-hydroxy-4-(5-{4-[5-(2-imidazol-1-yl-ethyl)-2-pyridin-3-yl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,240)N-hydroxy-4-(5-{4-[2-isopropyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,241)N-hydroxy-4-[5-(4-{2-isopropyl-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,242)N-hydroxy-4-(5-{4-[5-(2-imidazol-1-yl-ethyl)-2-isopropyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,243)N-hydroxy-4-[5-(4-{2-isopropyl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,244)N-hydroxy-4-[5-(4-{5-[2-(3-imidazol-1-yl-propylamino)-ethyl]-2-isopropyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,245)N-hydroxy-4-(5-{4-[2-isopropyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,246)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,247)N-hydroxy-4-[5-(4-{2-cyclohexyl-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,248)N-hydroxy-4-[5-(4-{2-cyclohexyl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,249)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,250)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-dimethylamino-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,251)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-dipropylamino-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,252)N-hydroxy-4-(5-{4-[2-cyclohexyl-5-(2-cyclopropylamino-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,253)N-hydroxy-4-[5-(4-{2-amino-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,254)N-hydroxy-4-(5-{4-[5-(2-morpholin-4-yl-ethyl)-2-phenyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,255)N-hydroxy-4-(5-{4-[2-ethyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,256)N-hydroxy-4-(5-{4-[2-ethyl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,257)N-hydroxy-4-(4-{4-[2-methyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-butoxy)-benzamidine,258)4-(5-{4-[2-cyclohexyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,259)4-(5-{4-[2-methyl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,260)N-hydroxy-4-(5-{4-[2-methylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,261)N-hydroxy-4-[5-(4-{2-methylamino-5-[2-(4-methyl-piperazin-1-yl)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,262)N-hydroxy-4-(5-{4-[2-methylamino-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,263)N-hydroxy-4-[5-(4-{2-methylamino-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,264)N-hydroxy-4-[5-(4-{5-[2-(3-imidazol-1-yl-propylamino)-ethyl]-2-methylamino-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,265)4-(5-{4-[2-methylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,266)N-hydroxy-4-(5-{4-[2-dimethylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,267)N-hydroxy-4-(5-{4-[2-dimethylamino-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,268)N-hydroxy-4-(5-{4-[2-(isobutyryl-methyl-amino)-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,269)N-hydroxy-4-(5-{4-[2-[benzyl-(2-morpholin-4-yl-ethyl)-amino]-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,270)N-hydroxy-4-(5-{4-[2-diethylamino-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,271)N-hydroxy-4-(5-{4-[2-[bis-(2-methoxy-ethyl)-amino]-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,272)N-hydroxy-4-(5-{4-[2-morpholin-4-yl-5-(2-morpholine-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,273)N-hydroxy-4-(5-{4-[2-morpholin-4-yl-5-(2-thiomorpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,274)N-hydroxy-4-[5-(4-{5-[2-(4-methyl-piperazin-1-yl)-ethyl]-2-morpholin-4yl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,275)N-hydroxy-4-[5-(4-{2-morpholin-4-yl-5-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,276)N-hydroxy-4-(5-{4-[5-(2-morpholin-4-yl-ethyl)-2-piperidin-1-yl-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,277)4-(5-{4-[2-morpholin-4-yl-5-(2-morpholin-4-yl-ethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,278)N-hydroxy-4-(5-{4-[5-(2-isobutyrylamino-ethyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,279)N-hydroxy-4-{5-[4-(5-{2-[isobutyl-(pyridin-3-carbonyl)-amino]-ethyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,280)N-hydroxy-4-{5-[4-(5-{2-[cyclopropyl-(pyridin-4-carbonyl)-amino]-ethyl}-2-isopropyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,281)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-{2-[cyclopropyl-(pyridin-3-carbonyl)-amino]-ethyl}-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,282)N-hydroxy-4-{5-[4-(5-methylcarbamoyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,283)N-hydroxy-4-{5-[4-(5-isopropylcarbamoyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,284)N-hydroxy-4-{5-[4-(5-{3-imidazol-1-yl-propylcarbamoyl}-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,285)N-hydroxy-4-{5-[4-(2-amino-5-methylcarbamoyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,286)N-hydroxy-4-{5-[4-(2-methyl-5-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,287)N-hydroxy-4-(5-{4-[2-methyl-5-(4-methyl-piperazin-1-yl)-thiazole-4-yl]-phenoxy}-pentyloxy)-benzamidine,288)N-hydroxy-4-{5-[4-(2-amino-5-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,289)N-hydroxy-4-(5-{4-[5-(4-methyl-piperazin-1-yl)-2-morpholin-4-yl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,290)N-hydroxy-4-{5-[4-(2,5-di-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,291)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-5-thiomorpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,292)N-hydroxy-4-{5-[4-(2-morpholin-4-yl-5-pyrolidin-1-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,293)N-hydroxy-4-{5-[4-(2-methyl-5-morpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,294)N-hydroxy-4-(5-{4-[2-methyl-5-(4-methyl-piperazin-1-ylmethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,295)N-hydroxy-4-{5-[4-(2-methyl-5-thiomorpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,296)N-hydroxy-4-{5-[4-(2-methyl-5-piperidin-1-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,297)N-hydroxy-4-{5-[4-(5-dimethylaminomethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,298)N-hydroxy-4-{5-[4-(5-butylaminomethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,299)N-hydroxy-4-(5-{4-[5-(isobutylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,300)N-hydroxy-4-(5-{4-[5-(tert-butylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,301)N-hydroxy-4-{5-[4-(2-methyl-5-propylaminomethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,302)N-hydroxy-4-[5-(4-{2-methyl-5-[(2-morpholin-4-yl-ethylamino)-methyl]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,303)N-hydroxy-4-[5-(4-{5-[(3-imidazol-1-yl-propylamino)-methyl]-2-methyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,304)N-hydroxy-4-{5-[4-(2-methyl-5-pyrolidin-1-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,305)N-hydroxy-4-{5-[4-(5-imidazol-1-ylmethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,306)N-hydroxy-4-(5-{4-[5-(benzylamino-methyl)-2-methyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,307)N-hydroxy-4-{5-[4-(5-cyclopropylaminomethyl-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,308)N-hydroxy-4-{5-[4-(2-methylamino-5-morpholin-4-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,309)N-hydroxy-4-(5-{4-[2-(methyl-pyridin-4-ylmethyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,310)N-hydroxy-4-[5-(4-{2-[(2-hydroxy-ethyl)-methyl-amino]-5-morpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,311)N-hydroxy-4-(5-{4-[2-(ethyl-methyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,312)N-hydroxy-4-(5-{4-[2-(benzyl-methyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,313)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-5-morpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,314)N-hydroxy-4-[5-(4-{2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-5-thiomorpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,315)N-hydroxy-4-[5-(4-{5-{[bis-(2-methoxy-ethyl)-amino]-methyl}-2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,316)N-hydroxy-4-(5-{4-[2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-5-(4-methyl-piperazin-1-ylmethyl)-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,317)N-hydroxy-4-[5-(4-{5-(isopropylamino-methyl)-2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,318)N-hydroxy-4-[5-(4-{5-[(2-methoxy-ethylamino)-methyl]-2-[methyl-(2-morpholin-4-yl-ethyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,319)N-hydroxy-4-[5-(4-{2-[(2-methoxy-ethyl)-methyl-amino]-5-morpholin-4-ylmethyl-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,320)N-hydroxy-4-(5-{4-[2-(methyl-propyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,321)N-hydroxy-4-(5-{4-[2-(methyl-pyridin-3-ylmethyl-amino)-5-morpholin-4-ylmethyl-thiazol-4-yl]-phenoxy}-pentyloxy)-benzamidine,322)N-hydroxy-4-{5-[4-(2-methyl-5-methylamino-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,323)N-hydroxy-4-[5-(4-{2-methyl-5-[(pyridin-4-carbonyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,324)N-hydroxy-4-[5-(4-{2-methyl-5-[(pyridin-3-carbonyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,325)N-hydroxy-4-[5-(4-{2-phenyl-5-[(pyridin-3-carbonyl)-amino]-thiazol-4-yl}-phenoxy)-pentyloxy]-benzamidine,326)N-hydroxy-4-{5-[4-(5-dimethylamino-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,327)N-hydroxy-4-{5-[4-(5-dimethylamino-2-phenyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,328)N-hydroxy-4-{5-[4-(2-cyclohexyl-5-dimethylamino-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,329)N-hydroxy-4-{5-[4-(2-methyl-5-[1,2,4]triazol-1-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,330)N-hydroxy-4-{5-[4-(5-amino-2-phenyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,331)N-hydroxy-4-{5-[4-(5-amino-2-methyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,332)N-hydroxy-4-{5-[4-(5-amino-2-pyridin-3-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,333)N-hydroxy-4-{5-[4-(5-amino-2-ethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,334)N-hydroxy-4-{5-[4-(5-amino-2-cyclohexyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,335)N-hydroxy-4-{5-[4-(2-methylamino-5-morpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,336)N-hydroxy-4-{5-[4-(2-morpholine-4-yl-5-morpholin-4-ylmethyl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine,and 337)N-hydroxy-4-{5-[4-(5-morpholin-4-yl-2-piperidin-1-yl-thiazol-4-yl)-phenoxy]-pentyloxy}-benzamidine.25. The method of claim 1, wherein the bisphosphonate of Formula 2 isselected from the group consisting of etidronic acid, clodronic acid,pamidronic acid, tiludronic acid, risedronic acid, minodronic acid,ibandronic acid, zoledronic acid and alendronic acid.
 26. The method ofclaim 1, wherein the prophylactic or therapeutic composition forosteoporosis is prepared in a form of combination formulation comprising(a) the benzamidine derivative represented by the following Formula 1 orsalt thereof, and (b) bisphosphonate represented by the followingFormula
 2. 27. The method of claim 1, wherein the prophylactic ortherapeutic composition for osteoporosis is prepared in a form of singleformulation comprising (a) the benzamidine derivative represented by thefollowing Formula 1 or salt thereof, and (b) bisphosphonate representedby the following Formula
 2. 28. The method of claim 1, wherein twosingle formulations comprising each of (a) the benzamidine derivativerepresented by the following Formula 1 or salt thereof, and (b)bisphosphonate represented by the following Formula 2 are provided inone kit.